Patient-specific Modeling of the Heart: Estimation of Ventricular Fiber Orientations

Patient-specific simulations of heart (dys)function aimed at personalizing cardiac therapy are hampered by the absence of in vivo imaging technology for clinically acquiring myocardial fiber orientations. The objective of this project was to develop a methodology to estimate cardiac fiber orientations from in vivo images of patient heart geometries. An accurate representation of ventricular geometry and fiber orientations was reconstructed, respectively, from high-resolution ex vivo structural magnetic resonance (MR) and diffusion tensor (DT) MR images of a normal human heart, referred to as the atlas. Ventricular geometry of a patient heart was extracted, via semiautomatic segmentation, from an in vivo computed tomography (CT) image. Using image transformation algorithms, the atlas ventricular geometry was deformed to match that of the patient. Finally, the deformation field was applied to the atlas fiber orientations to obtain an estimate of patient fiber orientations. The accuracy of the fiber estimates was assessed using six normal and three failing canine hearts. The mean absolute difference between inclination angles of acquired and estimated fiber orientations was 15.4 °. Computational simulations of ventricular activation maps and pseudo-ECGs in sinus rhythm and ventricular tachycardia indicated that there are no significant differences between estimated and acquired fiber orientations at a clinically observable level.The new insights obtained from the project will pave the way for the development of patient-specific models of the heart that can aid physicians in personalized diagnosis and decisions regarding electrophysiological interventions.     

Non-rigid deformation to include subject-specific detail in musculoskeletal models of CP children with proximal femoral deformity and its effect on muscle and contact forces during gait

To account for proximal femoral deformities in children with cerebral palsy (CP), subject-specific musculoskeletal models are needed. Non-rigid deformation (NRD) deforms generic onto personalized bone geometry and thereby transforms the muscle points. The goal of this study was to determine to what extent the models and simulation outcomes in CP patients differ when including subject-specific detail using NRD or Magnetic Resonance Imaging (MRI)-based models. The NRD models slightly overestimated hip contact forces compared to MRI models and differences in muscle point positions and moment arm lengths (MALs) remained, although differences were smaller than for the generic model.     

A comparative study of muscle force estimates using Huxley's and Hill's muscle model

Determination of muscle forces in individual muscles is often essential to assess optimal performance of human motion. Inverse dynamic methods based on the kinematics of the given motion and on the use of optimisation approach are the most widely used for muscle force estimation. The aim of this study was to estimate how the choice of muscle model influences predicted muscle forces. Huxley's (1957, Prog Biophys Biop Chem. 7: 255–318) and Hill's (1938, Proc R Soc B. 126: 136–195) muscle models were used for determination of muscle forces of two antagonistic muscles of the lower extremity during cycling. Huxley's model is a complex model that couples biochemical and physical processes with the microstructure of the muscle whereas the Hill's model is a phenomenological model. Muscle forces predicted by both models are within the same range. Huxley's model predicts more realistic patterns of muscle activation but it is computationally more demanding. Therefore, if the overall muscle forces are to be assessed, it is reasonable to use a simpler implementation based on Hill's model.     

Length-tension properties of ankle muscles in chronic human spinal cord injury

Contracture, or loss of range of motion (ROM) of a joint, is a common clinical problem in individuals with spinal cord injury (SCI). In order to measure the possible contribution of changes in muscle length to the loss of ankle ROM, the active force vs. angle curves for the tibialis anterior (TA) and gastrocnemiussoleus (GS) were measured in 20 participants, 10 with SCI, and 10 gender and age matched, neurologically intact (NI) individuals. Electrical stimuli were applied to the TA and GS motor nerves at incremented angles of the entire ROM of the ankle and the resulting ankle and knee torques were measured using a multi-axis load cell. The muscle forces of the TA and GS were calculated from the torque measurements using estimates of their respective moment arms and the resulting forces were plotted against joint angle. The force–angle relation for the GS at the ankle (GSA) was significantly shifted into plantar flexion in SCI subjects, compared to NI controls (t-test, p<0.001). Similar results were obtained based upon the GS knee (GSK) force–angle measurements (p<0.05). Conversely, no significant shift in the force–angle relation was found for the TA (p=0.138). Differences in the passive ROM were consistent with the force–angle changes. The ROM in the dorsiflexion direction was significantly smaller in SCI subjects compared to NI controls (p<0.05) while the plantar flexion ROM was not significantly different (p=0.114). Based upon these results, we concluded that muscle shortening is an important component of contracture in SCI.     

A biomechanical model of sagittal tongue bending

The human tongue is a structurally complex and extremely flexible organ. In order to better understand the mechanical basis for lingual deformations, we modeled a primitive movement of the tongue, sagittal tongue bending. We hypothesized that sagittal bending is a synergistic deformation derived from co-contraction of the longitudinalis and transversus muscles. Our model of tongue bending was based on classical bimetal strip theory, in which curvature is produced when one muscle layer contracts more so than another. Contraction was modulated via mismatched thermal expansion coefficients and temperature change (to simulate muscular contraction). Our results demonstrated that synergistic contraction produced curvature and strain results which were in better correspondence to empirical results derived from tagging MRI than were the results of contraction of the longitudinalis muscle alone. This fundamental reliance of tongue bending on the synergistic contraction of its intrinsic fibers supports the muscular hydrostat theory of tongue function.     

Can the sheep model fully represent the human model for the functional evaluation of cervical interbody fusion cages?

Sheep model is the most favourable choice for animal study for functional evaluation of the cervical fusion prostheses before clinical application; however, significantly large differences between sheep and human existed in terms of morphological characteristics and daily-activity motions. Questions should be raised as whether the differences between the two species have influence on the reliability of sheep model. Finite element models (FEM) of the cervical spinal system were built to characterize the differences between the two species with respect to the range of motion (ROM) and biomechanical behaviour, and experimental cadaver tests on both species were employed for validation purposes. Results indicate that sheep model represents the worst-case scenario of the human model with exaggerated stresses (up to 3 times more) and ROM (up to 10 times more). Moreover, sheep model is very sensitive to the variation of prostheses design, whilst human model does not, which denotes that the sheep model provides a rather amplified effect of a certain design for its biomechanical performance. Therefore, caution needs to be taken when sheep models were used as the animal model for functional evaluation over various design, and the FEM built in this study can be employed as an effective methodology for performance evaluation of cage prostheses of cervical spine.

     

An EMG-driven biomechanical model of the canine cervical spine

Due to the frequency of cervical spine injuries in canines, the purpose of this effort was to develop an EMG-driven dynamic model of the canine cervical spine to assess a biomechanical understanding that enables one to investigate the risk of neck disorders. A canine subject was recruited in this investigation in order to collect subject specific data. Reflective markers and a motion capture system were used for kinematic measurement; surface electrodes were used to record electromyography signals, and with the aid of force plate kinetics were recorded. A 3D model of the canine subject was reconstructed from an MRI dataset. Muscles lines of action were defined through a new technique with the aid of 3D white light scanner. The model performed well with a 0.73 weighted R² value in all three planes. The weighted average absolute error of the predicted moment was less than 10% of the external moment. The proposed model is a canine specific forward-dynamics model that precisely tracks the canine subject head and neck motion, calculates the muscle force generated from the twelve major moment producing muscles, and estimates resulting loads on specific spinal tissues.     

Rectus femoris and vastus intermedius fiber excursions predicted by three-dimensional muscle models

Computer models of the musculoskeletal system frequently represent the force-length behavior of muscle with a lumped-parameter model. Lumped-parameter models use simple geometric shapes to characterize the arrangement of muscle fibers and tendon; this may inaccurately represent changes in fiber length and the resulting force-length behavior, especially for muscles with complex architecture. The purpose of this study was to determine the extent to which the complex features of the rectus femoris and vastus intermedius architectures affect the fiber changes in length ("fiber excursions"). We created three-dimensional finite-element models of the rectus femoris and vastus intermedius muscles based on magnetic resonance (MR) images, and compared the fiber excursions predicted by the finite-element models with fiber excursions predicted by lumped-parameter models of these muscles. The finite-element models predicted rectus femoris fiber excursions (over a 100 degrees range of knee flexion) that varied from 55% to 70% of the excursion of the muscle-tendon unit and vastus intermedius fiber excursions that varied from 55% to 98% of the excursion muscle-tendon unit. In contrast, the lumped-parameter model of the rectus femoris predicted fiber excursions that were 86% of the excursion of the muscle-tendon unit and vastus intermedius fiber excursions that were 97% of the excursion of the muscle-tendon unit. These results suggest that fiber excursions of many fibers are overestimated in lumped-parameter models of these muscles. These new representations of muscle architecture can improve the accuracy of computer simulations of movement and provide insight into muscle design.     

Reduction of knee range of motion during continuous passive motion due to misaligned hip joint centre

When using continuous passive motion (CPM) devices, appropriate setting of the device and positioning of the patient are necessary to obtain maximum range of motion (ROM). In this study, the ROMs in both the knee joint and CPM device during CPM treatment were measured using a motion analysis system for three different CPM devices. Additionally, the trajectories of the angles at the knee for hip joint misalignments were evaluated using kinematic models of the three CPM devices. The results showed that discrepancies in ROM between the knee joints and the CPM device settings during CPM treatment were revealed regardless of the CPM device and that the effect of misalignment is dependent on the design of the CPM device. The present technology could be applied for the development of a better design configuration for the CPM device to reduce the discrepancy in ROM at the knee joint.     

Reduction of knee range of motion during continuous passive motion due to misaligned hip joint centre

When using continuous passive motion (CPM) devices, appropriate setting of the device and positioning of the patient are necessary to obtain maximum range of motion (ROM). In this study, the ROMs in both the knee joint and CPM device during CPM treatment were measured using a motion analysis system for three different CPM devices. Additionally, the trajectories of the angles at the knee for hip joint misalignments were evaluated using kinematic models of the three CPM devices. The results showed that discrepancies in ROM between the knee joints and the CPM device settings during CPM treatment were revealed regardless of the CPM device and that the effect of misalignment is dependent on the design of the CPM device. The present technology could be applied for the development of a better design configuration for the CPM device to reduce the discrepancy in ROM at the knee joint.     

A musculoskeletal model customized for squatting task

Most musculoskeletal models (MSKM) are designed to evaluate gait and running, which have limited range of motion (ROM). The purpose of this study was to examine the effect of wrapping surfaces (WS) at the knee and hip joints in a MSKM, on the muscle moment arms (MA) and activations during squatting. The MSKM was then customized by changing parameters of the original WS and by implementing additional WS. The WS prevent muscles from crossing into the bones, providing realistic muscle MA for large ROM. The modified MSKM is suitable for analysis up to 138° hip and 145° knee flexions.     

A 10-week stretching program increases strength in the contralateral muscle

It was questioned whether a unilateral stretching program would induce a crosstraining effect in the contralateral muscle. To test this, 13 untrained individuals participated in a 10-week stretching program while 12 other untrained individuals served as a control group. For the experimental group, the right calf muscle was stretched 4 times for 30 seconds, with a 30-second rest between stretches, 3 d·wk(-1) for 10 weeks. Strength, determined via 1 repetition maximum (1RM) unilateral standing toe raise, and range of motion (ROM) were measured pre-post. In the treatment group, the stretched calf muscle had a significant (p < 0.05) 8% increase in ROM, whereas the nonstretched calf muscle had a significant 1% decrease in ROM. The 1 RM of the stretched calf muscle significantly increased 29%, whereas the 1RM of the nonstretched calf muscle significantly increased 11%. In the control group, neither 1RM nor ROM changed for either leg. The results indicate that 10 weeks of stretching only the right calf will significantly increase the strength of both calves. Hence, chronic stretching can also induce a crosstraining effect for strength but not for the ROM. This study also validates earlier findings suggesting that stretching can elicit strength gains in untrained individuals.     

A micromechanical model of skeletal muscle to explore the effects of fiber and fascicle geometry

Computational models of muscle generally lump the material properties of connective tissue, muscle fibers, and muscle fascicles together into one constitutive relationship that assumes a transversely isotropic microstructure. These models do not take into account how variations in the microstructure of muscle affect its macroscopic material properties. The goal of this work was to develop micromechanical models of muscle to determine the effects of variations in muscle microstructure on the macroscopic constitutive behavior. We created micromechanical models at the fiber and fascicle levels based on histological cross-sections of two rabbit muscles, the rectus femoris (RF) and the soleus, to determine the effects of microstructure geometry (fiber and fascicle shapes) on the along-fiber shear modulus of muscle. The two fiber-level models predicted similar macroscopic shear moduli (within 13.5% difference); however, the two fascicle-level models predicted very different macroscopic shear moduli (up to 161% difference). We also used the micromechanical models to test the assumption that the macroscopic properties of muscle are transversely isotropic about the fiber (or fascicle) direction. The fiber-level models exhibited behavior consistent with the transverse isotropy assumption; however, the fascicle-level models exhibited transversely anisotropic behavior. Micromechanical models, combined with fiber and fiber bundle mechanical experiments, are needed to understand how normal or pathological variations in microstructure give rise to the observed macroscopic behavior of muscle.     

Predicting the influence of hip and lumbar flexibility on lifting motions using optimal control

Computational models of the human body coupled with optimization can be used to predict the influence of variables that cannot be experimentally manipulated. Here, we present a study that predicts the motion of the human body while lifting a box, as a function of flexibility of the hip and lumbar joints in the sagittal plane. We modeled the human body in the sagittal plane with joints actuated by pairs of agonist-antagonist muscle torque generators, and a passive hamstring muscle. The characteristics of a stiff, average and flexible person were represented by co-varying the lumbar range-of-motion, lumbar passive extensor-torque and the hamstring passive muscle-force. We used optimal control to solve for motions that simulated lifting a 10 kg box from a 0.3 m height. The solution minimized the total sum of the normalized squared active and passive muscle torques and the normalized passive hamstring muscle forces, over the duration of the motion. The predicted motion of the average lifter agreed well with experimental data in the literature. The change in model flexibility affected the predicted joint angles, with the stiffer models flexing more at the hip and knee, and less at the lumbar joint, to complete the lift. Stiffer models produced similar passive lumbar torque and higher hamstring muscle force components than the more flexible models. The variation between the motion characteristics of the models suggest that flexibility may play an important role in determining lifting technique.     

Validation of a personalized curved muscle model of the lumbar spine during complex dynamic exertions

Previous curved muscle models have typically examined their robustness only under simple, single-plane static exertions. In addition, the empirical validation of curved muscle models through an entire lumbar spine has not been fully realized. The objective of this study was to empirically validate a personalized biologically-assisted curved muscle model during complex dynamic exertions. Twelve subjects performed a variety of complex lifting tasks as a function of load weight, load origin, and load height. Both a personalized curved muscle model as well as a straight-line muscle model were used to evaluate the model’s fidelity and prediction of three-dimensional spine tissue loads under different lifting conditions. The curved muscle model showed better model performance and different spinal loading patterns through an entire lumbar spine compared to the straight-line muscle model. The curved muscle model generally showed good fidelity regardless of lifting condition. The majority of the 600 lifting tasks resulted in a coefficient of determination (R²) greater than 0.8 with an average of 0.83, and the average absolute error less than 15% between measured and predicted dynamic spinal moments. As expected, increased load and asymmetry were generally found to significantly increase spinal loads, demonstrating the ability of the model to differentiate between experimental conditions. A curved muscle model would be useful to estimate precise spine tissue loads under realistic circumstances. This precise assessment tool could aid in understanding biomechanical causal pathways for low back pain.     

Modeling left ventricular dynamics with characteristic deformation modes

A computationally efficient method is described for simulating the dynamics of the left ventricle (LV) in three dimensions. LV motion is represented as a combination of a limited number of deformation modes, chosen to represent observed cardiac motions while conserving volume in the LV wall. The contribution of each mode to wall motion is determined by a corresponding time-dependent deformation variable. The principle of virtual work is applied to these deformation variables, yielding a system of ordinary differential equations for LV dynamics, including effects of muscle fiber orientations, active and passive stresses, and surface tractions. Passive stress is governed by a transversely isotropic elastic model. Active stress acts in the fiber direction and incorporates length–tension and force–velocity properties of cardiac muscle. Preload and afterload are represented by lumped vascular models. The variational equations and their numerical solutions are verified by comparison to analytic solutions of the strong form equations. Deformation modes are constructed using Fourier series with an arbitrary number of terms. Greater numbers of deformation modes increase deformable model resolution but at increased computational cost. Simulations of normal LV motion throughout the cardiac cycle are presented using models with 8, 23, or 46 deformation modes. Aggregate quantities that describe LV function vary little as the number of deformation modes is increased. Spatial distributions of stress and strain change as more deformation modes are included, but overall patterns are conserved. This approach yields three-dimensional simulations of the cardiac cycle on a clinically relevant time-scale.

     

Responses of ankle plantar-flexors to various inhibitions of muscular activities in rats]

Effects of hindlimb suspension, tenotomy, denervation, and/or the combination of these models on plantar-flexors were studied in adult rats. Suspension-induced atrophy was not promoted by addition of tenotomy. But the magnitude of the atrophy was advanced if denervation or both denervation and tenotomy were combined with 5-day hindlimb suspension. Similar effects were noted in the cross-sectional area of single muscle fibers, especially of slow-twitch fibers. A shift of muscle fiber type from slow- to fast-twitch type was also induced mainly in soleus. The atrophy and fiber transformation were closely associated with a passive shortening of muscle due to the plantar-flexion of ankle and/or tenotomy and a disappeared electrical activity caused by denervation. The fiber atrophy, but not the shift of fiber type, was further advanced by the combination of tenotomy and denervation. It is suggested that muscle atrophy is caused by the decreased fiber size and protein content. The water content was also reduced proportionally.     

Laplace-based modeling of fiber orientation in the tongue

Mechanical modeling of tongue deformation plays a significant role in the study of breathing, swallowing, and speech production. In the absence of internal joints, fiber orientations determine the direction of sarcomeric contraction and have great influence over real and simulated tissue motion. However, subject-specific experimental observations of fiber distribution are difficult to obtain; thus, models of fiber distribution are generally used in mechanical simulations. This paper describes modeling of fiber distribution using solutions of Laplace equations and compares the effectiveness of this approach against tractography from diffusion tensor magnetic resonance imaging. The experiments included qualitative comparison of streamlines from the fiber model against experimental tractography, as well as quantitative differences between biomechanical simulations focusing in the region near the genioglossus. The model showed good overall agreement in terms of fiber directionality and muscle positioning when compared to subject-specific imaging results and the literature. The angle between the fiber distribution model against tractography in the genioglossus and geniohyoid muscles averaged \(22^{\circ }\) likely due to experimental noise. However, kinematic responses were similar between simulations with modeled fibers versus experimentally obtained fibers; average discrepancy in surface displacement ranged from 1 to 7 mm, and average strain residual magnitude ranged from \(4\times 10^{-3}\) to 0.2. The results suggest that, for simulation purposes, the modeled fibers can act as a reasonable approximation for the tongue’s fiber distribution. Also, given its agreement with the global tongue anatomy, the approach may be used in model-based reconstruction of displacement tracking and diffusion results.     

Muscle activity and spine load during pulling exercises: Influence of stable and labile contact surfaces and technique coaching

This study examined pulling exercises performed on stable surfaces and unstable suspension straps. Specific questions included: which exercises challenged particular muscles, what was the magnitude of resulting spine load, and did technique coaching influence results. Fourteen males performed pulling tasks while muscle activity, external force, and 3D body segment motion were recorded. These data were processed and input to a sophisticated and anatomically detailed 3D model that used muscle activity and body segment kinematics to estimate muscle force, in this way the model was sensitive to each individual’s choice of motor control for each task. Muscle forces and linked segment joint loads were used to calculate spine loads. There were gradations of muscle activity and spine load characteristics to every task. It appears that suspension straps alter muscle activity less in pulling exercises, compared to studies reporting on pushing exercises. The chin-up and pull-up exercises created the highest spine load as they required the highest muscle activation, despite the body “hanging” under tractioning gravitational load. Coaching shoulder centration through retraction increased spine loading but undoubtedly adds proximal stiffness. An exercise atlas of spine compression was constructed to help with the decision making process of exercise choice for an individual.