Passive Tissue Properties Research Articles

Uncertainty Quantification of Regional Cardiac Tissue Properties in Arrhythmogenic Cardiomyopathy Using Adaptive Multiple Importance Sampling.

Introduction: Computational models of the cardiovascular system are widely used to simulate cardiac (dys)function. Personalization of such models for patient-specific simulation of cardiac function remains challenging. Measurement uncertainty affects accuracy of parameter estimations. In this study, we present a methodology for patient-specific estimation and uncertainty quantification of parameters in the closed-loop CircAdapt model of the human heart and circulation using echocardiographic deformation imaging. Based on patient-specific estimated parameters we aim to reveal the mechanical substrate underlying deformation abnormalities in patients with arrhythmogenic cardiomyopathy (AC).Methods: We used adaptive multiple importance sampling to estimate the posterior distribution of regional myocardial tissue properties. This methodology is implemented in the CircAdapt cardiovascular modeling platform and applied to estimate active and passive tissue properties underlying regional deformation patterns, left ventricular volumes, and right ventricular diameter. First, we tested the accuracy of this method and its inter- and intraobserver variability using nine datasets obtained in AC patients. Second, we tested the trueness of the estimation using nine in silico generated virtual patient datasets representative for various stages of AC. Finally, we applied this method to two longitudinal series of echocardiograms of two pathogenic mutation carriers without established myocardial disease at baseline.Results: Tissue characteristics of virtual patients were accurately estimated with a highest density interval containing the true parameter value of 9% (95% CI [0–79]). Variances of estimated posterior distributions in patient data and virtual data were comparable, supporting the reliability of the patient estimations. Estimations were highly reproducible with an overlap in posterior distributions of 89.9% (95% CI [60.1–95.9]). Clinically measured deformation, ejection fraction, and end-diastolic volume were accurately simulated. In presence of worsening of deformation over time, estimated tissue properties also revealed functional deterioration.Conclusion: This method facilitates patient-specific simulation-based estimation of regional ventricular tissue properties from non-invasive imaging data, taking into account both measurement and model uncertainties. Two proof-of-principle case studies suggested that this cardiac digital twin technology enables quantitative monitoring of AC disease progression in early stages of disease.

Local and Non-local Effects of Foam Rolling on Passive Soft Tissue Properties and Spinal Excitability.

In sports and clinical settings, roller massage (RM) interventions are used to acutely increase range of motion (ROM); however, the underlying mechanisms are unclear. Apart from changes in soft tissue properties (i.e., reduced passive stiffness), neurophysiological alterations such as decreased spinal excitability have been described. However, to date, no study has investigated both jointly. The purpose of this trial was to examine RM’s effects on neurophysiological markers and passive tissue properties of the plantar flexors in the treated (ROLL) and non-treated (NO-ROLL) leg. Fifteen healthy individuals (23 ± 3 years, eight females) performed three unilateral 60-s bouts of calf RM. This procedure was repeated four times on separate days to allow independent assessments of the following outcomes without reciprocal interactions: dorsiflexion ROM, passive torque during passive dorsiflexion, shear elastic modulus of the medial gastrocnemius muscle, and spinal excitability. Following RM, dorsiflexion ROM increased in both ROLL (+19.7%) and NO-ROLL (+13.9%). Similarly, also passive torque at dorsiflexion ROM increased in ROLL (+15.0%) and NO-ROLL (+15.2%). However, there were no significant changes in shear elastic modulus and spinal excitability (p > 0.05). Moreover, significant correlations were observed between the changes in DF ROM and passive torque at DF ROM in both ROLL and NO-ROLL. Changes in ROM after RM appear to be the result of sensory changes (e.g., passive torque at DF ROM), affecting both rolled and non-rolled body regions. Thus, therapists and exercise professionals may consider applying remote treatments if local loading is contraindicated.

Generation of Monophasic Action Potentials and Intermediate Forms

The monophasic action potential (MAP) is a near replica of the transmembrane potential recorded when an electrode is pushed firmly against cardiac tissue. Despite its many practical uses, the mechanism of MAP signal generation and the reason it is so different from unipolar recordings are not completely known and are a matter of controversy. In this work, we describe a method to simulate realistic MAP and intermediate forms, which are multiphasic electrograms different from an ideal MAP. The key ideas of our method are the formation of compressed zones and junctional spaces—regions of the extracellular and bath or blood pool directly in contact with electrodes that exhibit a pressure-induced reduction in electrical conductivity—and the presence of a complex network of passive components that acts as a high-pass filter to distort and attenuate the signal that reaches the recording amplifier. The network is formed by the interaction between the passive tissue properties and the double-layer capacitance of electrodes. The MAP and intermediate forms reside on a continuum of signals, which can be generated by the change of the model parameters. Our model helps to decipher the mechanisms of signal generation and can lead to a better design for electrodes, recording amplifiers, and experimental setups.

The habitual motion path theory: Evidence from cartilage volume reductions in the knee joint after 75\u2009minutes of running

The habitual motion path theory predicts that humans tend to maintain their habitual motion path (HMP) during locomotion. The HMP is the path of least resistance of the joints defined by an individual’s musculoskeletal anatomy and passive tissue properties. Here we tested whether participants with higher HMP deviation and whether using footwear that increases HMP deviation during running show higher reductions of knee joint articular cartilage volume after 75 minutes of running. We quantified knee joint articular cartilage volumes before and after the run using a 3.0-Tesla MRI. We performed a 3D movement analysis of runners in order to quantify their HMP from a two-legged squat motion and the deviation from the HMP when running in different footwear conditions. We found significantly more cartilage volume reductions in the medial knee compartment and patella for participants with higher HMP deviation. We also found higher cartilage volume reductions on the medial tibia when runners wore a shoe that maximized their HMP deviation compared with the shoe that minmized their HMP deviation. Runners might benefit from reducing their HMP deviation and from selecting footwear by quantifying HMP deviation in order to minimize joint cartilage loading in sub-areas of the knee.

Quantitative tissue parameters of Achilles tendon and plantar fascia in healthy subjects using a handheld myotonometer

ObjectiveThe aim of the study was to examine the quantitative tissue properties of the Achilles tendon and plantar fascia using a handheld, non-invasive MyotonPRO device, in order to generate normal values and examine the biomechanical relationship of both structures. DesignProspective study of a large, healthy sample population. ParticipantsThe study sample included 207 healthy subjects (87 males and 120 females) for the Achilles tendon and 176 healthy subjects (73 males and 103 females) for the plantar fascia. For the correlations of the tissue parameters of the Achilles tendon and plantar fascia an intersection of both groups was formed which included 150 healthy subjects (65 males and 85 females). InterventionsAll participants were measured in a prone position. Consecutive measurements of the Achilles tendon and plantar fascia were performed by MyotonPRO device at defined sites. ResultsFor the left and right Achilles tendons and plantar fasciae all five MyotonPRO parameters (Frequency [Hz], Decrement, Stiffness [N/m], Creep and Relaxation Time [ms]) were calculated of healthy males and females. The correlation of the tissue parameters of the Achilles tendon and plantar fascia showed a significant positive correlation of all parameters on the left as well as on the right side. ConclusionsThe MyotonPRO is a feasible device for easy measurement of passive tissue properties of the Achilles tendon and plantar fascia in a clinical setting. The generated normal values of the Achilles tendon and plantar fascia are important for detecting abnormalities in patients with Achilles tendinopathy or plantar fasciitis in the future. Biomechanically, both structures are positively correlated. This may provide new aspects in the diagnostics and therapy of plantar fasciitis and Achilles tendinopathy.

An EMG-assisted modeling approach to assess passive lumbar tissue loading in vivo during trunk bending

Lower back pain (LBP) is a condition with high prevalence and high cost both in the United States and around the world. The magnitude of mechanical loading on spine is strongly associated with the occurrence of LBP. Previously, to assess spinal loading, biologically assisted biomechanical models were developed to estimate trunk muscle contraction forces. Loadings on lumbar passive tissues are estimated using anatomical models. However, despite the substantial individual variability in lumbar ligament geometry and viscoelastic properties, the existing anatomical models do not account for these differences. As such, the accuracy of model prediction is compromised especially when mid to full range of trunk motions are involved. This paper describes a new modeling approach to assess lumbar passive tissue loading with the consideration of individual differences in lumbar passive tissue properties. A data set that has trunk bending data from 13 human participants was analyzed; on average, lumbar passive tissue contributes to ∼89% of the total spinal compression force at fully flexed trunk postures; the estimated spinal tissue loadings were in feasible ranges as reported from previous cadaver studies; the estimated spinal loadings were also mostly in agreement with results from previous in vivo studies.

The influence of a semi-reclined seated posture on head and neck kinematics and muscle activity while reading a tablet computer

Increased tablet computer usage calls for a proper understanding of potential injury risks from these devices. The purpose of this study was to assess the influence of tablet computer reading postures on head and neck flexion and muscle activity. Nineteen participants completed read a tablet computer in four different postures (standard computer monitor, tablet on a desk, tablet in the lap, semi-reclined with tablet in the lap). Reading the tablet in a semi-reclined trunk posture with the tablet in one's lap increased (p < 0.001) neck flexion angle (71.6%ROM) relative to reading from the standard computer monitor (6.39%ROM). Head flexion in the semi-reclined posture (19.7%ROM) and muscle activity (8.88%MVC) were similar to when reading from a standard computer monitor. Despite potentially reducing the gravitational moment produced by the head, the semi-reclined position could still compromise the force capabilities of the neck extensor musculature and result in increased strain on the passive tissues of the spine. Future work should assess how the semi-reclined position influences cervical intervertebral angles and passive tissue properties of the cervical spine. Overall, more research needs to be conducted on thoracic spine kinematics while reading a tablet computer.

Personalized Computer Simulation of Diastolic Function in Heart Failure

The search for a parameter representing left ventricular relaxation from non-invasive and invasive diagnostic tools has been extensive, since heart failure (HF) with preserved ejection fraction (HF-pEF) is a global health problem. We explore here the feasibility using patient-specific cardiac computer modeling to capture diastolic parameters in patients suffering from different degrees of systolic HF. Fifty eight patients with idiopathic dilated cardiomyopathy have undergone thorough clinical evaluation, including cardiac magnetic resonance imaging (MRI), heart catheterization, echocardiography, and cardiac biomarker assessment. A previously-introduced framework for creating multi-scale patient-specific cardiac models has been applied on all these patients. Novel parameters, such as global stiffness factor and maximum left ventricular active stress, representing cardiac active and passive tissue properties have been computed for all patients. Invasive pressure measurements from heart catheterization were then used to evaluate ventricular relaxation using the time constant of isovolumic relaxation Tau (τ). Parameters from heart catheterization and the multi-scale model have been evaluated and compared to patient clinical presentation. The model parameter global stiffness factor, representing diastolic passive tissue properties, is correlated significantly across the patient population with τ. This study shows that multi-modal cardiac models can successfully capture diastolic (dys) function, a prerequisite for future clinical trials on HF-pEF.

The effect of intrinsic muscular nonlinearities on the energetics of locomotion in a computational model of an anguilliform swimmer

Animals move through their environments using muscles to produce force. When an animal׳s nervous system activates a muscle, the muscle produces different amounts of force depending on its length, its shortening velocity, and its time history of force production. These muscle forces interact with forces from passive tissue properties and forces from the external environment. Using an integrative computational model that couples an elastic, actuated model of an anguilliform, lamprey-like swimmer with a surrounding Navier–Stokes fluid, we study the effects of this coupling between the muscle force and the body motion. Swimmers with different forms of this coupling can achieve similar motions, but use different amounts of energy. The velocity dependence is the most important property of the ones we considered for reducing energy costs and helping us to stabilize oscillations. These effects are strongly influenced by how rapidly the muscle deactivates; if force decays too slowly, muscles on opposite sides of the body end up fighting each other, increasing energy cost. Work-dependent deactivation, an effect that causes a muscle to deactivate more rapidly if it has recently produced mechanical work, works together with the velocity dependence to reduce the energy cost of swimming.

Local Gradients in Electrotonic Loading Modulate the Local Effective Refractory Period: Implications for Arrhythmogenesis in the Infarct Border Zone.

Ectopic electrical activity that originates in the peri-infarct region can give rise to potentially lethal re-entrant arrhythmias. The spatial variation in electrotonic loading that results from structural remodelling in the infarct border zone may increase the probability that focal activity will trigger electrical capture, but this has not previously been investigated systematically. This study uses in-silico experiments to examine the structural modulation of effective refractory period on ectopic beat capture. Informed by 3-D reconstructions of myocyte organization in the infarct border zone, a region of rapid tissue expansion is abstracted to an idealized representation. A novel metric is introduced that defines the local electrotonic loading as a function of passive tissue properties and boundary conditions. The effective refractory period correlates closely with local electrotonic loading, while the action potential duration, conduction, and upstroke velocity reduce in regions of increasing electrotonic load. In the presence of focal ectopic stimuli, spatial variation in effective refractory period can cause unidirectional conduction block providing a substrate for reentrant arrhythmias. Consequently, based on the observed results, a possible novel mechanism for arrhythmogenesis in the infarct border zone is proposed.

Exploring susceptibility to atrial and ventricular arrhythmias resulting from remodeling of the passive electrical properties in the heart: a simulation approach.

Under diseased conditions, remodeling of the cardiac tissue properties (“passive properties”) takes place; these are aspects of electrophysiological behavior that are not associated with active ion transport across cell membranes. Remodeling of the passive electrophysiological properties most often results from structural remodeling, such as gap junction down-regulation and lateralization, fibrotic growth infiltrating the myocardium, or the development of an infarct scar. Such structural remodeling renders atrial or ventricular tissue as a major substrate for arrhythmias. The current review focuses on these aspects of cardiac arrhythmogenesis. Due to the inherent complexity of cardiac arrhythmias, computer simulations have provided means to elucidate interactions pertinent to this spatial scale. Here we review the current state-of-the-art in modeling atrial and ventricular arrhythmogenesis as arising from the disease-induced changes in the passive tissue properties, as well as the contributions these modeling studies have made to our understanding of the mechanisms of arrhythmias in the heart. Because of the rapid advance of structural imaging methodologies in cardiac electrophysiology, we chose to present studies that have used such imaging methodologies to construct geometrically realistic models of cardiac tissue, or the organ itself, where the regional remodeling properties of the myocardium can be represented in a realistic way. We emphasize how the acquired knowledge can be used to pave the way for clinical applications of cardiac organ modeling under the conditions of structural remodeling.

Altered flexion-relaxation responses exist during asymmetric trunk flexion movements among persons with unilateral lower-limb amputation

Repetitive exposures to altered gait and movement following lower-limb amputation (LLA) have been suggested to contribute to observed alterations in passive tissue properties and neuromuscular control in/surrounding the lumbar spine. These alterations, in turn, may affect the synergy between passive and active tissues during trunk movements. Eight males with unilateral LLA and eight non-amputation controls completed quasi-static trunk flexion–extension movements in seven distinct conditions of rotation in the transverse plane: 0° (sagittally-symmetric), ±15°, ±30°, and ±45° (sagittally-asymmetric). Electromyographic (EMG) activity of the bilateral lumbar erector spinae and lumbar kinematics were simultaneously recorded. Peak lumbar flexion and EMG-off angles were determined, along with the difference (“DIFF”) between these two angles and the magnitude of peak normalized EMG activities. Persons with unilateral LLA exhibited altered and asymmetric synergies between active and passive trunk tissues during both sagittally-symmetric and -asymmetric trunk flexion movements. Specifically, decreased and asymmetric passive contributions to trunk movements were compensated with increases in the magnitude and duration of active trunk muscle responses. Such alterations in trunk passive and active neuromuscular responses may result from repetitive exposures to abnormal gait and movement subsequent to LLA, and may increase the risk for LBP in this population.

Using sitting as a component of job rotation strategies: Are lifting/lowering kinetics and kinematics altered following prolonged sitting

Workers are often required to perform manual materials handling tasks immediately following periods of prolonged sitting either as a secondary job component of as different tasks in a job rotation strategy. The goal of this investigation was to determine if changes to low-back kinetics and/or kinematics occurred during repetitive lifting/lowering exertions following extended seated exposures. Upper body kinematics, lumbar spine flexion angle, pelvic orientation and bilateral muscle activity from the external abdominal obliques and lumbar erector spinae were recorded for 8 males and 8 females while they alternated between sessions of repetitive lifting/lowering and prolonged sitting. Upper body kinematics were used as inputs to a linked segment model to compute low-back flexion/extension moments, compression, and shear. Peak lumbar flexion was reduced by 1.8° during the lifting/lowering exertions following the first hour of sitting which consequently led to a reduction of approximately 50 N in the reaction anteroposterior shear forces. Sitting postures were consistent with previously reported data. The reduced shear loads during repetitive lift/lower exertions following prolonged sitting may be a consequence of alterations in passive tissue properties which could alter the risk of low-back injury, although future research is required to examine the biomechanical significance of this finding. Changes to both kinematics and kinetics were minimal suggesting that using prolonged sitting as a component of a task series in job rotation does not alter the risk present when combined with repetitive lifting tasks.

Ontogenetic changes in the structural stiffness of the tailstock of bottlenose dolphins (Tursiops truncatus)

Late-term fetal bottlenose dolphins (Tursiops truncatus) are bent ventrolaterally en utero, requiring extreme flexibility of the axial skeleton and associated soft tissues. At birth, neonatal dolphins must immediately swim to the surface to breath, yet the dorsoventral oscillations used during locomotion may be compromised by the lateral flexibility evident in the fetus. The unique fetal position of dolphins, coupled with their need to swim at birth, places conflicting mechanical demands on the tailstock. Our previous research demonstrated that neonatal dolphins possess laterally placed, axial muscles that are functionally specialized to actively maintain the straightened posture of the tailstock. Here, we investigated the development of passive lateral stability in the tailstock of bottlenose dolphins by performing whole-body bending tests on an ontogenetic series of stranded dolphin specimens (N=15), including fetuses, neonates and juveniles (total length 58-171 cm). Structural stiffness increased, while overall body curvature decreased, with increasing body length. Scaling analyses suggest that increased structural stiffness is due to increases in size and probably changes in the passive material properties of the tailstock through ontogeny. The neutral zone was approximately constant with increasing size, while the relative neutral zone (neutral zone/total length) decreased. The lateral stability of the tailstock appears to be controlled by a combination of active and passive systems and the role of these systems varies through ontogeny. While neonates use active, muscular mechanisms to limit lateral deformations of the tailstock, the stability of the maturing tailstock is due primarily to its passive tissue properties.

A detailed biomechanical finite element tongue model

For research on surgical modifications of the tongue, e.g., implants for treatment of sleep apnea, we built a detailed finite element model of the human tongue, to experimentally estimate and investigate muscle activations corresponding to observed movement data, and to study possible effects of tissue modifications. Most of the extrinsic and all intrinsic muscles of the tongue are represented as parametrized volumes within the tongue, and muscle fiber directions are specified by a tangent in curvilinear coordinate systems of parametric solids that overlay each muscle region. Fiber regions of different muscles may overlap, for example, for the transverse and vertical intrinsic muscles. Mixed Ogden type hyper-elastic models of strain energy density are used to represent passive tissue properties, and active contraction in muscle fibers is emulated by changing externally specified activation parameters in an anisotropic component of the strain energy density. The activation can vary over time and in its spatial distribution over a muscle, which is accomplished by specifying center point and spread of a Gaussian distribution in the muscle region. The tongue model is realized as a finite element implementation with large displacement/large strain calculations using incompressible 8-node elements in a commercial FE code (Marc by MSC-Software).

New analysis for the study of the muscle function in the human oesophagus

The aim was to further develop a method for studying the active and passive tissue properties in the human oesophagus. An impedance planimetric probe with a bag for distension was placed in the distal oesophagus in 14 healthy volunteers. Distension was done at an infusion rate of 25 mL min(-1) with and without the administration of the antimuscarinic drug butylscopolamine. The flow was reversed when moderate pain was experienced by the subject. The total and the passive tension showed an exponential behaviour as function of the change in radius. The active tensions increased until they reached a maximum point. The active tension decreased after the maximum until the distension was stopped shortly after due to the pain. The change in tension during distension-induced contractions (the afterload) was plotted as function of the precontraction radius (the preload). The human oesophagus behaves in a manner known from in vitro studies on muscle strips and exhibits a muscle diagram similar to that in the heart, i.e. the larger the initial muscle length during distension (within limits), the greater the contraction force.