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  • 1.
    Biasetti, Jacopo
    et al.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Hussain, Fazle
    Department of Mechanical Engineering, University of Houston, Houstohn, TX, USA.
    Gasser, T. Christian
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Blood flow and coherent vortices in the normal and aneurysmatic aortas: a fluid dynamical approach to intraluminal thrombus formation2011In: Journal of the Royal Society Interface, ISSN 1742-5689, E-ISSN 1742-5662, Vol. 8, no 63, p. 1449-1461Article in journal (Refereed)
    Abstract [en]

    Abdominal aortic aneurysms (AAAs) are frequently characterized by the development of an intra-luminal thrombus (ILT), which is known to have multiple biochemical and biomechanical implications. Development of the ILT is not well understood, and shear-stress-triggered activation of platelets could be the first step in its evolution. Vortical structures (VSs) in the flow affect platelet dynamics, which motivated the present study of a possible correlation between VS and ILT formation in AAAs. VSs educed by the lambda(2)-method using computational fluid dynamics simulations of the backward-facing step problem, normal aorta, fusiform AAA and saccular AAA were investigated. Patient-specific luminal geometries were reconstructed from computed tomography scans, and Newtonian and Carreau-Yasuda models were used to capture salient rheological features of blood flow. Particularly in complex flow domains, results depended on the constitutive model. VSs developed all along the normal aorta, showing that a clear correlation between VSs and high wall shear stress (WSS) existed, and that VSs started to break up during late systole. In contrast, in the fusiform AAA, large VSs developed at sites of tortuous geometry and high WSS, occupying the entire lumen, and lasting over the entire cardiac cycle. Downward motion of VSs in the AAA was in the range of a few centimetres per cardiac cycle, and with a VS burst at that location, the release (from VSs) of shear-stress-activated platelets and their deposition to the wall was within the lower part of the diseased artery, i.e. where the thickest ILT layer is typically observed. In the saccular AAA, only one VS was found near the healthy portion of the aorta, while in the aneurysmatic bulge, no VSs occurred. We present a fluid-dynamics-motivated mechanism for platelet activation, convection and deposition in AAAs that has the potential of improving our current understanding of the pathophysiology of fluid-driven ILT growth.

  • 2.
    Biasetti, Jacopo
    et al.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.).
    Spazzini, Pier Giorgio
    Hedin, Ulf
    Gasser, T. Christian
    Synergy between shear-induced migration and secondary flows on red blood cells transport in arteries: considerations on oxygen transport2014In: Journal of the Royal Society Interface, ISSN 1742-5689, E-ISSN 1742-5662, Vol. 11, no 97, p. 20140403-Article in journal (Refereed)
    Abstract [en]

    Shear-induced migration of red blood cells (RBCs) is a well-known phenomenon characterizing blood flow in the small vessels (micrometre to millimetre size) of the cardiovascular system. In large vessels, like the abdominal aorta and the carotid artery (millimetre to centimetre size), the extent of this migration and its interaction with secondary flows has not been fully elucidated. RBC migration exerts its influence primarily on platelet concentration, oxygen transport and oxygen availability at the luminal surface, which could influence vessel wall disease processes in and adjacent to the intima. Phillips' shear-induced particle migration model, coupled to the Quemada viscosity model, was employed to simulate the macroscopic behaviour of RBCs in four patient-specific geometries: a normal abdominal aorta, an abdominal aortic aneurysm (AAA), a normal carotid bifurcation and a stenotic carotid bifurcation. Simulations show a migration of RBCs from the near-wall region with a lowering of wall haematocrit (volume fraction of RBCs) on the posterior side of the normal aorta and on the lateral-external side of the iliac arteries. A marked migration is observed on the outer wall of the carotid sinus, along the common carotid artery and in the carotid stenosis. No significant migration is observed in the AAA. The spatial and temporal patterns of wall haematocrit are correlated with the near-wall shear layer and with the secondary flows induced by the vessel curvature. In particular, secondary flows accentuate the initial lowering in RBC near-wall concentration by convecting RBCs from the inner curvature side to the outer curvature side. The results reinforce data in literature showing a decrease in oxygen partial pressure on the inner curvature wall of the carotid sinus induced by the presence of secondary flows. The lowering of wall haematocrit is postulated to induce a decrease in oxygen availability at the luminal surface through a diminished concentration of oxyhaemoglobin, hence contributing, with the reported lowered oxygen partial pressure, to local hypoxia.

  • 3. Comellas, E.
    et al.
    Gasser, T. Christian
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.).
    Bellomo, F. J.
    Oller, S.
    A homeostatic-driven turnover remodelling constitutive model for healing in soft tissues2016In: Journal of the Royal Society Interface, ISSN 1742-5689, E-ISSN 1742-5662, Vol. 13, no 116, article id 20151081Article in journal (Refereed)
    Abstract [en]

    Remodelling of soft biological tissue is characterized by interacting biochemical and biomechanical events, which change the tissue's microstructure, and, consequently, its macroscopic mechanical properties. Remodelling is a well-defined stage of the healing process, and aims at recovering or repairing the injured extracellular matrix. Like other physiological processes, remodelling is thought to be driven by homeostasis, i.e. it tends to re-establish the properties of the uninjured tissue. However, homeostasis may never be reached, such that remodelling may also appear as a continuous pathological transformation of diseased tissues during aneurysm expansion, for example. A simple constitutive model for soft biological tissues that regards remodelling as homeostatic-driven turnover is developed. Specifically, the recoverable effective tissue damage, whose rate is the sum of a mechanical damage rate and a healing rate, serves as a scalar internal thermodynamic variable. In order to integrate the biochemical and biomechanical aspects of remodelling, the healing rate is, on the one hand, driven by mechanical stimuli, but, on the other hand, subjected to simple metabolic constraints. The proposed model is formulated in accordance with continuum damage mechanics within an open-system thermodynamics framework. The numerical implementation in an in-house finite-element code is described, particularized for Ogden hyperelasticity. Numerical examples illustrate the basic constitutive characteristics of the model and demonstrate its potential in representing aspects of remodelling of soft tissues. Simulation results are verified for their plausibility, but also validated against reported experimental data.

  • 4. Croze, Ottavio A.
    et al.
    Sardina, Gaetano
    KTH, School of Engineering Sciences (SCI), Mechanics. KTH, School of Engineering Sciences (SCI), Centres, Linné Flow Center, FLOW.
    Ahmed, Mansoor
    KTH, School of Engineering Sciences (SCI), Mechanics. KTH, School of Engineering Sciences (SCI), Centres, Linné Flow Center, FLOW.
    Bees, Martin A.
    Brandt, Luca
    KTH, School of Engineering Sciences (SCI), Mechanics. KTH, School of Engineering Sciences (SCI), Centres, Linné Flow Center, FLOW.
    Dispersion of swimming algae in laminar and turbulent channel flows: consequences for photobioreactors2013In: Journal of the Royal Society Interface, ISSN 1742-5689, E-ISSN 1742-5662, Vol. 10, no 81, p. 20121041-Article in journal (Refereed)
    Abstract [en]

    Shear flow significantly affects the transport of swimming algae in suspension. For example, viscous and gravitational torques bias bottom-heavy cells to swim towards regions of downwelling fluid (gyrotaxis). It is necessary to understand how such biases affect algal dispersion in natural and industrial flows, especially in view of growing interest in algal photobioreactors. Motivated by this, we here study the dispersion of gyrotactic algae in laminar and turbulent channel flows using direct numerical simulation (DNS) and a previously published analytical swimming dispersion theory. Time-resolved dispersion measures are evaluated as functions of the Peclet and Reynolds numbers in upwelling and downwelling flows. For laminar flows, DNS results are compared with theory using competing descriptions of biased swimming cells in shear flow. Excellent agreement is found for predictions that employ generalized Taylor dispersion. The results highlight peculiarities of gyrotactic swimmer dispersion relative to passive tracers. In laminar downwelling flow the cell distribution drifts in excess of the mean flow, increasing in magnitude with Peclet number. The cell effective axial diffusivity increases and decreases with Peclet number (for tracers it merely increases). In turbulent flows, gyrotactic effects are weaker, but discernable and manifested as non-zero drift. These results should have a significant impact on photobioreactor design.

  • 5. Federico, Salvatore
    et al.
    Gasser, T. Christian
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.).
    Nonlinear elasticity of biological tissues with statistical fibre orientation2010In: Journal of the Royal Society Interface, ISSN 1742-5689, E-ISSN 1742-5662, Vol. 7, no 47, p. 955-966Article in journal (Refereed)
    Abstract [en]

    The elastic strain energy potential for nonlinear fibre-reinforced materials is customarily obtained by superposition of the potentials of the matrix and of each family of fibres. Composites with statistically oriented fibres, such as biological tissues, can be seen as being reinforced by a continuous infinity of fibre families, the orientation of which can be represented by means of a probability density function defined on the unit sphere (i.e. the solid angle). In this case, the superposition procedure gives rise to an integral form of the elastic potential such that the deformation features in the integral, which therefore cannot be calculated a priori. As a consequence, an analytical use of this potential is impossible. In this paper, we implemented this integral form of the elastic potential into a numerical procedure that evaluates the potential, the stress and the elasticity tensor at each deformation step. The numerical integration over the unit sphere is performed by means of the method of spherical designs, in which the result of the integral is approximated by a suitable sum over a discrete subset of the unit sphere. As an example of application, we modelled the collagen fibre distribution in articular cartilage, and used it in simulating displacement-controlled tests: the unconfined compression of a cylindrical sample and the contact problem in the hip joint.

  • 6.
    Gasser, T. Christian
    et al.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.).
    Ogden, R. W.
    Holzapfel, G. A.
    Hyperelastic modelling of arterial layers with distributed collagen fibre orientations2006In: Journal of the Royal Society Interface, ISSN 1742-5689, E-ISSN 1742-5662, Vol. 3, no 6, p. 15-35Article, review/survey (Refereed)
    Abstract [en]

    Constitutive relations are fundamental to the solution of problems in continuum mechanics, and are required in the study of, for example, mechanically dominated clinical interventions involving soft biological tissues. Structural continuum constitutive models of arterial layers integrate information about the tissue morphology and therefore allow investigation of the interrelation between structure and function in response to mechanical loading. Collagen fibres are key ingredients in the structure of arteries. In the media (the middle layer of the artery wall) they are arranged in two helically distributed families with a small pitch and very little dispersion in their orientation (i.e. they are aligned quite close to the circumferential direction). By contrast, in the adventitial and intimal layers, the orientation of the collagen fibres is dispersed, as shown by polarized light microscopy of stained arterial tissue. As a result, continuum models that do not account for the dispersion are not able to capture accurately the stress-strain response of these layers. The purpose of this paper, therefore, is to develop a structural continuum framework that is able to represent the dispersion of the collagen fibre orientation. This then allows the development of a new hyperelastic free-energy function that is particularly suited for representing the anisotropic elastic properties of adventitial and intimal layers of arterial walls, and is a generalization of the fibre-reinforced structural model introduced by Holzapfel & Gasser (Holzapfel & Gasser 2001 Comput. Meth. Appl. Mech. Eng. 190, 4379-4403) and Holzapfel et al. (Holzapfel et al. 2000 J. Elast. 61, 1-48). The model incorporates an additional scalar structure parameter that characterizes the dispersed collagen orientation. An efficient finite element implementation of the model is then presented and numerical examples show that the dispersion of the orientation of collagen fibres in the adventitia of human iliac arteries has a significant effect on their mechanical response.

  • 7.
    Giordano, Chiara
    et al.
    KTH, School of Technology and Health (STH), Medical Engineering, Neuronic Engineering.
    Kleiven, Svein
    KTH, School of Technology and Health (STH), Medical Engineering, Neuronic Engineering.
    Connecting Fractional Anisotropy from Medical Images with Mechanical Anisotropy of a Hyperviscoelastic Fibre-reinforced Constitutive Model for Brain Tissue2014In: Journal of the Royal Society Interface, ISSN 1742-5689, E-ISSN 1742-5662, Vol. 11, no 91, p. 20130914-Article in journal (Refereed)
    Abstract [en]

    Brain tissue modelling has been an active area of research for years. Brain matter does not follow the constitutive relations for common materials and loads applied to the brain turn into stresses and strains depending on tissue local morphology. In this work, a hyperviscoelastic fibre-reinforced anisotropic law is used for computational brain injury prediction. Thanks to a fibrere-inforcement dispersion parameter, this formulation accounts for anisotropic features and heterogeneities of the tissue owing to different axon alignment. The novelty of the work is the correlation of the material mechanical anisotropy with fractional anisotropy (FA) from diffusion tensor images. Finite-element (FE) models are used to investigate the influence of the fibre distribution for different loading conditions. In the case of tensile-compressive loads, the comparison between experiments and simulations highlights the validity of the proposed FA-k correlation. Axon alignment affects the deformation predicted by FE models and, when the strain in the axonal direction is large with respect to the maximum principal strain, decreased maximum deformations are detected. It is concluded that the introduction of fibre dispersion information into the constitutive law of brain tissue affects the biofidelity of the simulations.

  • 8.
    Holme, Petter
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Model validation of simple-graph representations of metabolism2009In: Journal of the Royal Society Interface, ISSN 1742-5689, E-ISSN 1742-5662, Vol. 6, no 40, p. 1027-1034Article in journal (Refereed)
    Abstract [en]

    The large-scale properties of chemical reaction systems, such as metabolism, can be studied with graph-based methods. To do this, one needs to reduce the information, lists of chemical reactions, available in databases. Even for the simplest type of graph representation, this reduction can be done in several ways. We investigate different simple network representations by testing how well they encode information about one biologically important network structure-network modularity (the propensity for edges to be clustered into dense groups that are sparsely connected between each other). To achieve this goal, we design a model of reaction systems where network modularity can be controlled and measure how well the reduction to simple graphs captures the modular structure of the model reaction system. We find that the network types that best capture the modular structure of the reaction system are substrate-product networks (where substrates are linked to products of a reaction) and substance networks (with edges between all substances participating in a reaction). Furthermore, we argue that the proposed model for reaction systems with tunable clustering is a general framework for studies of how reaction systems are affected by modularity. To this end, we investigate statistical properties of the model and find, among other things, that it recreates correlations between degree and mass of the molecules.

  • 9. Holme, Petter
    et al.
    Huss, M.
    Role-similarity based functional prediction in networked systems: application to the yeast proteome2005In: Journal of the Royal Society Interface, ISSN 1742-5689, E-ISSN 1742-5662, Vol. 2, no 4, p. 327-333Article in journal (Refereed)
    Abstract [en]

    We propose a general method to predict functions of vertices where (i) the wiring of the network is somehow related to the vertex functionality and (ii) a fraction of the vertices are functionally classified. The method is influenced by role-similarity measures of social network analysis. The two versions of our prediction scheme axe tested on model networks where the functions of the vertices are designed to match their network surroundings. We also apply these methods to the proteome of the yeast Saccharomyces cerevisiae and find the results compatible with more specialized methods.

  • 10.
    Holzapfel, Gerhard A.
    et al.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Solid Mechanics (Div.).
    Ogden, R. W.
    Modelling the layer-specific three-dimensional residual stresses in arteries, with an application to the human aorta2010In: Journal of the Royal Society Interface, ISSN 1742-5689, E-ISSN 1742-5662, Vol. 7, no 46, p. 787-799Article in journal (Refereed)
    Abstract [en]

    This paper provides the first analysis of the three-dimensional state of residual stress and stretch in an artery wall consisting of three layers (intima, media and adventitia), modelled as a circular cylindrical tube. The analysis is based on experimental results on human aortas with non-atherosclerotic intimal thickening documented in a recent paper by Holzapfel et al. (Holzapfel et al. 2007 Ann. Biomed. Eng. 35, 530-545 (doi:10.1007/s10439-006-9252-z)). The intima is included in the analysis because it has significant thickness and load-bearing capacity, unlike in a young, healthy human aorta. The mathematical model takes account of bending and stretching in both the circumferential and axial directions in each layer of the wall. Previous analysis of residual stress was essentially based on a simple application of the opening-angle method, which cannot accommodate the three-dimensional residual stretch and stress states observed in experiments. The geometry and nonlinear kinematics of the intima, media and adventitia are derived and the associated stress components determined explicitly using the nonlinear theory of elasticity. The theoretical results are then combined with the mean numerical values of the geometrical parameters and material constants from the experiments to illustrate the three-dimensional distributions of the stretches and stresses throughout the wall. The results highlight the compressive nature of the circumferential stress in the intima, which may be associated with buckling of the intima and its delamination from the media, and show that the qualitative features of the stretch and stress distributions in the media and adventitia are unaffected by the presence or absence of the intima. The circumferential residual stress in the intima increases significantly as the associated residual deformation in the intima increases while the corresponding stress in the media (which is compressive at its inner boundary and tensile at its outer boundary) is only slightly affected. The theoretical framework developed herein enables the state of residual stress to be calculated directly, serves to improve insight into the mechanical response of an unloaded artery wall and can be extended to accommodate more general geometries, kinematics and states of residual stress as well as more general constitutive models.

  • 11.
    Martufi, Giampaolo
    et al.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Gasser, T. Christian
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Turnover of fibrillar collagen in soft biological tissue with application to the expansion of abdominal aortic aneurysms2012In: Journal of the Royal Society Interface, ISSN 1742-5689, E-ISSN 1742-5662, Vol. 9, no 77, p. 3366-3377Article in journal (Refereed)
    Abstract [en]

    A better understanding of the inherent properties of vascular tissue to adapt to its mechanical environment is crucial to improve the predictability of biomechanical simulations. Fibrillar collagen in the vascular wall plays a central role in tissue adaptation owing to its relatively short lifetime. Pathological alterations of collagen turnover may fail to result in homeostasis and could be responsible for abdominal aortic aneurysm (AAA) growth at later stages of the disease. For this reason our previously reported multiscale constitutive framework (Martufi, G. & Gasser, T. C. 2011 J. Biomech. 44, 2544-2550 (doi:10.1016/j.jbiomech.2011.07.015)) has been enriched by a collagen turnover model. Specifically, the framework's collagen fibril level allowed a sound integration of vascular wall biology, and the impact of collagen turnover on the macroscopic properties of AAAs was studied. To this end, model parameters were taken from the literature and/or estimated from clinical follow-up data of AAAs (on average 50.7 mm-large). Likewise, the in vivo stretch of the AAA wall was set, such that 10 per cent of collagen fibres were engaged. Results showed that the stretch spectrum, at which collagen fibrils are deposed, is the most influential parameter, i.e. it determines whether the vascular geometry grows, shrinks or remains stable over time. Most importantly, collagen turnover also had a remarkable impact on the macroscopic stress field. It avoided high stress gradients across the vessel wall, thus predicted a physiologically reasonable stress field. Although the constitutive model could be successfully calibrated to match the growth of small AAAs, a rigorous validation against experimental data is crucial to further explore the model's descriptive and predictive capabilities.

  • 12.
    Nikolaev, Nikolai
    et al.
    Loughborough University.
    Liu, Yang
    Loughborough University.
    Hussein, Husnah
    Loughborough University.
    Williams, David J
    Loughborough university.
    The sensitivity of human mesenchymal stem cells to vibration and cold storage conditions representative of cold transportation2012In: Journal of the Royal Society Interface, ISSN 1742-5689, E-ISSN 1742-5662, Vol. 9, no 75, p. 2503-2515Article in journal (Refereed)
    Abstract [en]

    In the current study, the mechanical and hypothermic damage induced by vibration and cold storage on human mesenchymal stem cells (hMSCs) stored at 2-8°C was quantified by measuring the total cell number and cell viability after exposure to vibration at 50 Hz (peak acceleration 140 m s-2 and peak displacement 1.4 mm), 25 Hz (peak acceleration 140 m s-2, peak displacement 5.7 mm), 10 Hz (peak acceleration 20 m s-2, peak displacement 5.1 mm) and cold storage for several durations. To quantify the viability of the cells, in addition to the trypan blue exclusion method, the combination of annexin V-FITC and propidium iodide was applied to understand the mode of cell death. Cell granularity and a panel of cell surface markers for stemness, including CD29, CD44, CD105 and CD166, were also evaluated for each condition. It was found that hMSCs were sensitive to vibration at 25 Hz, with moderate effects at 50 Hz and no effects at 10 Hz. Vibration at 25 Hz also increased CD29 and CD44 expression. The study further showed that cold storage alone caused a decrease in cell viability, especially after 48 h, and also increased CD29 and CD44 and attenuated CD105 expressions. Cell death would most likely be the consequence of membrane rupture, owing to necrosis induced by cold storage. The sensitivity of cells to different vibrations within the mechanical system is due to a combined effect of displacement and acceleration, and hMSCs with a longer cold storage duration were more susceptible to vibration damage, indicating a coupling between the effects of vibration and cold storage.

  • 13. Polzer, Stanislav
    et al.
    Gasser, T. Christian
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Solid Mechanics (Div.).
    Biomechanical rupture risk assessment of abdominal aortic aneurysms based on a novel probabilistic rupture risk index2015In: Journal of the Royal Society Interface, ISSN 1742-5689, E-ISSN 1742-5662, Vol. 12, no 113, article id 20150852Article in journal (Refereed)
    Abstract [en]

    A rupture risk assessment is critical to the clinical treatment of abdominal aortic aneurysm (AAA) patients. The biomechanical AAA rupture risk assessment quantitatively integrates many known AAA rupture risk factors but the variability of risk predictions due to model input uncertainties remains a challenging limitation. This study derives a probabilistic rupture risk index (PRRI). Specifically, the uncertainties in AAA wall thickness and wall strength were considered, and wall stress was predicted with a state-of-the-art deterministic biomechanical model. The discriminative power of PRRI was tested in a diameter-matched cohort of ruptured (n = 7) and intact (n = 7) AAAs and compared to alternative risk assessment methods. Computed PRRI at 1.5 mean arterial pressure was significantly (p = 0.041) higher in ruptured AAAs (20.21(s.d. 14.15%)) than in intact AAAs (3.71(s.d. 5.77)%). PRRI showed a high sensitivity and specificity (discriminative power of 0.837) to discriminate between ruptured and intact AAA cases. The underlying statistical representation of stochastic data of wall thickness, wall strength and peak wall stress had only negligible effects on PRRI computations. Uncertainties in AAA wall stress predictions, the wide range of reported wall strength and the stochastic nature of failure motivate a probabilistic rupture risk assessment. Advanced AAA biomechanical modelling paired with a probabilistic rupture index definition as known from engineering risk assessment seems to be superior to a purely deterministic approach.

  • 14. Schriefl, Andreas J.
    et al.
    Reinisch, Andreas J.
    Sankaran, Sethuraman
    Pierce, David M.
    Holzapfel, Gerhard A.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.).
    Quantitative assessment of collagen fibre orientations from two-dimensional images of soft biological tissues2012In: Journal of the Royal Society Interface, ISSN 1742-5689, E-ISSN 1742-5662, Vol. 9, no 76, p. 3081-3093Article in journal (Refereed)
    Abstract [en]

    In this work, we outline an automated method for the extraction and quantification of material parameters characterizing collagen fibre orientations from two-dimensional images. Morphological collagen data among different length scales were obtained by combining the established methods of Fourier power spectrum analysis, wedge filtering and progressive regions of interest splitting. Our proposed method yields data from which we can determine parameters for computational modelling of soft biological tissues using fibre-reinforced constitutive models and gauge the length scales most appropriate for obtaining a physically meaningful measure of fibre orientations, which is representative of the true tissue morphology of the two-dimensional image. Specifically, we focus on three parameters quantifying different aspects of the collagen morphology: first, using maximum-likelihood estimation, we extract location parameters that accurately determine the angle of the principal directions of the fibre reinforcement (i.e. the preferred fibre directions); second, using a dispersion model, we obtain dispersion parameters quantifying the collagen fibre dispersion about these principal directions; third, we calculate the weighted error entropy as a measure of changes in the entire fibre distributions at different length scales, as opposed to their average behaviour. With fully automated imaging techniques (such as multiphoton microscopy) becoming increasingly popular (which often yield large numbers of images to analyse), our method provides an ideal tool for quickly extracting mechanically relevant tissue parameters which have implications for computational modelling (e.g. on the mesh density) and can also be used for the inhomogeneous modelling of tissues.

  • 15. Schriefl, Andreas J.
    et al.
    Wolinski, Heimo
    Regitnig, Peter
    Kohlwein, Sepp D.
    Holzapfel, Gerhard A.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.).
    An automated approach for three-dimensional quantification of fibrillar structures in optically cleared soft biological tissues2013In: Journal of the Royal Society Interface, ISSN 1742-5689, E-ISSN 1742-5662, Vol. 10, no 80, p. 20120760-Article in journal (Refereed)
    Abstract [en]

    We present a novel approach allowing for a simple, fast and automated morphological analysis of three-dimensional image stacks (z-stacks) featuring fibrillar structures from optically cleared soft biological tissues. Five non-atherosclerotic tissue samples from human abdominal aortas were used to outline the multi-purpose methodology, applicable to various tissue types. It yields a three-dimensional orientational distribution of relative amplitudes, representing the original collagen fibre morphology, identifies regions of isotropy where no preferred fibre orientations are observed and determines structural parameters throughout anisotropic regions for the analysis and numerical modelling of biomechanical quantities such as stress and strain. Our method combines optical tissue clearing with second-harmonic generation imaging, Fourier-based image analysis and maximum-likelihood estimation for distribution fitting. With a new sample preparation method for arteries, we present, for the first time to our knowledge, a continuous three-dimensional distribution of collagen fibres throughout the entire thickness of the aortic wall, revealing novel structural and organizational insights into the three arterial layers.

  • 16. Schriefl, Andreas J.
    et al.
    Zeindlinger, Georg
    Pierce, David M.
    Regitnig, Peter
    Holzapfel, Gerhard A.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.).
    Determination of the layer-specific distributed collagen fibre orientations in human thoracic and abdominal aortas and common iliac arteries2012In: Journal of the Royal Society Interface, ISSN 1742-5689, E-ISSN 1742-5662, Vol. 9, no 71, p. 1275-1286Article in journal (Refereed)
    Abstract [en]

    The established method of polarized microscopy in combination with a universal stage is used to determine the layer-specific distributed collagen fibre orientations in 11 human non-atherosclerotic thoracic and abdominal aortas and common iliac arteries (63 +/- 15.3 years, mean +/- s.d.). A dispersion model is used to quantify over 37 000 recorded fibre angles from tissue samples. The study resulted in distinct fibre families, fibre directions, dispersion and thickness data for each layer and all vessels investigated. Two fibre families were present for the intima, media and adventitia in the aortas, with often a third and sometimes a fourth family in the intima in the respective axial and circumferential directions. In all aortas, the two families were almost symmetrically arranged with respect to the cylinder axis, closer to the axial direction in the adventitia, closer to the circumferential direction in the media and in between in the intima. The same trend was found for the intima and adventitia of the common iliac arteries; however, there was only one preferred fibre alignment present in the media. In all locations and layers, the observed fibre orientations were always in the tangential plane of the walls, with no radial components and very small dispersion through the wall thickness. A wider range of in-plane fibre orientations was present in the intima than in the media and adventitia. The mean total wall thickness for the aortas and the common iliac artery was 1.39 and 1.05 mm, respectively. For the aortas, a slight thickening of the intima and a thinning of the media in increasingly distal regions were observed. A clear intimal thickening was present distal to the branching of the celiac arteries. All data, except for the media of the common iliac arteries, showed two prominent collagen fibre families for all layers so that two-fibre family models seem most appropriate.

  • 17.
    Widengren, Jerker
    KTH, School of Engineering Sciences (SCI), Applied Physics, Experimental Biomolecular Physics.
    Fluorescence-based transient state monitoring for biomolecular spectroscopy and imaging2010In: Journal of the Royal Society Interface, ISSN 1742-5689, E-ISSN 1742-5662, Vol. 7, no 49, p. 1135-1144Article, review/survey (Refereed)
    Abstract [en]

    To increase read-out speed, sensitivity or specificity, an often applied strategy in fluorescence-based biomolecular spectroscopy and imaging is to simultaneously record two or more of the fluorescence parameters: intensity, lifetime, polarization or wavelength. This review highlights how additional, to-date largely unexploited, information can be extracted by monitoring long-lived, photo-induced transient states of organic dyes and their dynamics. Two major approaches are presented, where the transient state information is obtained either from fluorescence fluctuation analysis or by recording the time-averaged fluorescence response to a time-modulated excitation. The two approaches combine the detection sensitivity of the fluorescence signal with the environmental sensitivity of the long-lived transient states. For both techniques, proof-of-principle experiments are reviewed, and advantages, limitations and possible applications for biomolecular cellular biology studies are discussed.

  • 18. Zhou, Joseph Xu
    et al.
    Aliyu, M. D. S.
    Aurell, Erik
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Huang, Sui
    Quasi-potential landscape in complex multi-stable systems2012In: Journal of the Royal Society Interface, ISSN 1742-5689, E-ISSN 1742-5662, Vol. 9, no 77, p. 3539-3553Article in journal (Refereed)
    Abstract [en]

    The developmental dynamics of multicellular organisms is a process that takes place in a multi-stable system in which each attractor state represents a cell type, and attractor transitions correspond to cell differentiation paths. This new understanding has revived the idea of a quasi-potential landscape, first proposed by Waddington as a metaphor. To describe development, one is interested in the 'relative stabilities' of N attractors (N > 2). Existing theories of state transition between local minima on some potential landscape deal with the exit part in the transition between two attractors in pair-attractor systems but do not offer the notion of a global potential function that relates more than two attractors to each other. Several ad hoc methods have been used in systems biology to compute a landscape in non-gradient systems, such as gene regulatory networks. Here we present an overview of currently available methods, discuss their limitations and propose a new decomposition of vector fields that permits the computation of a quasi-potential function that is equivalent to the Freidlin-Wentzell potential but is not limited to two attractors. Several examples of decomposition are given, and the significance of such a quasi-potential function is discussed.

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