Marie-Christine Ho Ba Tho

Measurement of liver stiffness with two imaging techniques: Magnetic resonance elastography and ultrasound elastometry

To cross‐validate the magnetic resonance elastography (MRE) technique with a clinical device, based on an ultrasound elastometry system called Fibroscan.

On the Relative Relevance of Subject-Specific Geometries and Degeneration-Specific Mechanical Properties for the Study of Cell Death in Human Intervertebral Disk Models

Capturing patient- or condition-specific intervertebral disk (IVD) properties in finite element models is outmost important in order to explore how biomechanical and biophysical processes may interact in spine diseases. However, disk degenerative changes are often modeled through equations similar to those employed for healthy organs, which might not be valid. As for the simulated effects of degenerative changes, they likely depend on specific disk geometries. Accordingly, we explored the ability of continuum tissue models to simulate disk degenerative changes. We further used the results in order to assess the interplay between these simulated changes and particular IVD morphologies, in relation to disk cell nutrition, a potentially important factor in disk tissue regulation. A protocol to derive patient-specific computational models from clinical images was applied to different spine specimens. In vitro, IVD creep tests were used to optimize poro-hyperelastic input material parameters in these models, in function of the IVD degeneration grade. The use of condition-specific tissue model parameters in the specimen-specific geometrical models was validated against independent kinematic measurements in vitro. Then, models were coupled to a transport-cell viability model in order to assess the respective effects of tissue degeneration and disk geometry on cell viability. While classic disk poro-mechanical models failed in representing known degenerative changes, additional simulation of tissue damage allowed model validation and gave degeneration-dependent material properties related to osmotic pressure and water loss, and to increased fibrosis. Surprisingly, nutrition-induced cell death was independent of the grade-dependent material properties, but was favored by increased diffusion distances in large IVDs. Our results suggest that in situ geometrical screening of IVD morphology might help to anticipate particular mechanisms of disk degeneration.

Analysis of Liver Viscosity Behavior as a Function of Multifrequency Magnetic Resonance Elastography (MMRE) Postprocessing

To analyze the relevance of the viscosity measurement as a liver diagnostic marker.

ASSESSMENT OF PARAMETER UNCERTAINTY IN RIGID MUSCULOSKELETAL SIMULATION USING A PROBABILISTIC APPROACH

Experimental investigation coupled with numerical simulations is commonly used for solving multi-physical problems. In the field of biomechanics, in which the aim is to understand the mechanics of living system, the main difficulties are to provide experimental data reflecting the multi-physical behavior of the system of interest. These experimental data are used as input data for numerical simulations to quantify output responses through physical and/or biological laws expressed by constitutive mathematical equations. However, uncertainties on the experimentally available data exist from factors such as human variability and differences in protocols parameters and techniques. Thus, the true values of these data could never be experimentally measured. The objective of this study was to develop a modeling workflow to assess and account for the parameter uncertainty in rigid musculoskeletal simulation. A generic musculoskeletal model was used. Data uncertainties of the right thigh mass, physiological cross-sectional area (pCSA) and muscle tension coefficient of the rectus femoris were accounted to estimate their effect on the joint moment and muscle force computing, respectively. A guideline was developed to fuse data from multiple sources into a sample variation space leading to establish input data distribution. Uncertainty propagation was performed using Monte Carlo and most probable point methods. A high degree of sensitivity of 0.98 was noted for the effect of thigh mass uncertainty on the hip joint moment using inverse dynamics method. A strong deviation of rectus femoris muscle force (around 260 N) was found under effect of pCSA and muscle tension coefficient on the force estimation using static optimization method. Accounting parameter uncertainty into rigid musculoskeletal simulation plays an essential role in the evaluation of the confidence in the model outputs. Thus, simulation outcome may be computed and represented in a more reliable manner with a global range of plausible values.

ESTIMATION OF MUSCLE FORCE DERIVED FROM IN VIVO MR ELASTOGRAPHY TESTS: A PRELIMINARY STUDY

The objective is to estimate the vastus medialis (VM) muscle force from multifrequency magnetic resonance elastography (MMRE) tests and two different rheological models (Voigt and springpot). Healthy participants (N = 13) underwent multifrequency (70, 90 and 110 Hz) magnetic resonance elastography MMRE tests. Thus, in vivo experimental elastic (μ) properties of the VM in passive and active (20% MVC) conditions were characterized. Moreover, the muscle viscosity (η) was determined with Voigt and springpot rheological models, in both muscle states. Subsequently, the VM muscle forces were calculated with a generic musculoskeletal model (OpenSIM) where the active and passive shear moduli (μ) were implemented. The viscosity measured with the two rheological models increased when the muscle is contracted. During the stance and the swing phases, the VM tensile forces decrease and the VM force was lower with the springpot model. It can be noted that during the swing phase, the muscle forces estimated from springpot model showed a higher standard deviation compared to the Voigt model. This last result may indicate a strong sensitivity of the muscle force to the change of active and passive contractile components in the swing phase of gait. This study provides for the first time an estimation of the muscle tensile forces for lower limb, during human motion, from in vivo experimental muscle mechanical properties. The assessment of individualized muscle forces during motion is valuable for finite element models, increasing the patient specific parameters. This novel muscle database will be of use for the clinician to better elucidate the muscle pathophysiology and to better monitor the effects of the muscle disease.

ASSESSMENT OF MECHANICAL PROPERTIES OF HUMAN OSTEON LAMELLAE EXHIBITING VARIOUS DEGREES OF MINERALIZATION BY NANOINDENTATION

Background: Cortical bone analysis has been investigated at the macroscopic level with mechanical tests and imaging techniques, but few studies have been done at the microscopic level (osteons). The purpose of this study is to measure the elastic modulus of thick lamellae of osteons exhibiting different degrees of mineralization. This study aims to provide clinicians with a better understanding of bone remodeling and help in assessing the different stages of bone healing. Methods: Six femoral human samples (5 mm × 5 mm × 5 mm) were cut transversally along the length of a human femur. Scanning electron micrographs were produced to reflect the composition of the microstructure. Three types of osteons were selected: white (high mineralization), gray (intermediate mineralization), and dark (low mineralization) osteons. Nanoindentation tests were performed on three locations of the thick lamella located in the middle of each osteon. The mechanical test induced three holdings and unloadings with a constant holding of 10 s. The maximal force was 2500 μN, which induced a maximal depth of about 400 nm. Results: Elastic modulus (E) and hardness (H) for the white (N = 61), gray (N = 17), and dark (N = 39) osteons were Ewhite = 21.30 GPa ± 3.00 GPa and Hwhite = 0.55 GPa ± 0.15 GPa, Egray = 19.27 GPa ± 1.78 GPa and Hgray = 0.41 GPa ± 0.09 GPa, and Edark = 12.95 GPa × 2.66 GPa and Hdark = 0.30 GPa ± 0.10 GPa, respectively. The variation of elastic properties within a lamella was approximately 2.6 GPa, depending on the level of mineralization. Conclusions: These results demonstrate the inhomogeneity of the lamella, suggesting that both the orientation of collagen fibers and the degree of mineralization may vary within the lamella. Our study shows a large range of elastic properties and hardness, reflecting different degrees of osteon mineralization.

Identification process based on shear wave propagation within a phantom using finite element modelling and magnetic resonance elastography

Magnetic resonance elastography (MRE), based on shear wave propagation generated by a specific driver, is a non-invasive exam performed in clinical practice to improve the liver diagnosis. The purpose was to develop a finite element (FE) identification method for the mechanical characterisation of phantom mimicking soft tissues investigated with MRE technique. Thus, a 3D FE phantom model, composed of the realistic MRE liver boundary conditions, was developed to simulate the shear wave propagation with the software ABAQUS. The assumptions of homogeneity and elasticity were applied to the FE phantom model. Different ranges of mesh size, density and Poissons ratio were tested in order to develop the most representative FE phantom model. The simulated wave displacement was visualised with a dynamic implicit analysis. Subsequently, an identification process was performed with a cost function and an optimisation loop provided the optimal elastic properties of the phantom. The present identification process was validated on a phantom model, and the perspective will be to apply this method on abdominal tissues for the set-up of new clinical MRE protocols that could be applied for the follow-up of the effects of treatments.

A CONSISTENT DATA FUSION APPROACH FOR UNCERTAINTY QUANTIFICATION IN RIGID MUSCULOSKELETAL SIMULATION

Uncertainty quantification in rigid musculoskeletal modeling is essential to analyze the risks related to the simulation outcomes. Data fusion from multiple sources is a potential solution to reduce data uncertainties. This present study aimed at proposing a new data fusion rule leading to a more consistent and coherent data for uncertainty quantification. Moreover, a new uncertainty representation was developed using imprecise probability approach. A biggest maximal coherent subsets (BMCS) operator was defined to fuse interval-valued data ranges from multiple sources. Fusion-based probability-box structure was developed to represent the data uncertainty. Case studies were performed for uncertainty propagation through inverse dynamics and static optimization algorithms. Hip joint moment and muscle force estimation were computed under effect of the uncertainties of thigh mass and muscle properties. Respective p-boxes of these properties were generated. Regarding the uncertainty propagation analysis, correlation coefficients showed a very good value (R=1) for the proposed fusion operator according to classical operators. Muscle force variation of the rectus femoris was computed. Peak-to-peak (i.e., difference between maximal values) rectus femoris forces showed deviations of 55N and 40N for the first and second peaks, respectively. The development of the new fusion operator and fusion-based probability-box leads to a more consistent uncertainty quantification. This allows the estimation of risks associated with the simulation outcomes under input data uncertainties for rigid musculoskeletal modeling and simulation.

Comparison of patient-specific computational models vs. clinical follow-up, for adjacent segment disc degeneration and bone remodelling after spinal fusion

Spinal fusion is a standard surgical treatment for patients suffering from low back pain attributed to disc degeneration. However, results are somewhat variable and unpredictable. With fusion the kinematic behaviour of the spine is altered. Fusion and/or stabilizing implants carrying considerable load and prevent rotation of the fused segments. Associated with these changes, a risk for accelerated disc degeneration at the adjacent levels to fusion has been demonstrated. However, there is yet no method to predict the effect of fusion surgery on the adjacent tissue levels, i.e. bone and disc. The aim of this study was to develop a coupled and patient-specific mechanoregulated model to predict disc generation and changes in bone density after spinal fusion and to validate the results relative to patient follow-up data. To do so, a multiscale disc mechanoregulation adaptation framework was developed and coupled with a previously developed bone remodelling algorithm. This made it possible to determine extra cellular matrix changes in the intervertebral disc and bone density changes simultaneously based on changes in loading due to fusion surgery. It was shown that for 10 cases the predicted change in bone density and degeneration grade conforms reasonable well to clinical follow-up data. This approach helps us to understand the effect of surgical intervention on the adjacent tissue remodelling. Thereby, providing the first insight for a spine surgeon as to which patient could potentially be treated successfully by spinal fusion and in which patient has a high risk for adjacent tissue changes.

HETEROGENEITY OF TIME-DEPENDENT MECHANICAL PROPERTIES OF HUMAN CORTICAL BONE AT THE MICRO SCALE

Background: Remodeling process affects the mineral content of osteons and imparts heterogeneity through secondary mineralization; the aim of the present study is to assess the elastic and plastic time-dependent mechanical properties of osteons reflecting different mineral content as well as interstitial tissue of human femoral cortical bone by nanoindentation. Methods: Four trapezoiform blocks approximately 3mm thick were cut from the distal end of different human femoral diaphysis. Osteons with different apparent mineral degrees were classified by means of gray levels imaging using Environmental Scanning Electron Microscopy (ESEM). Nanoindentation tests were performed in the longitudinal direction of the bone axis using a four-stage protocol (load-hold-unload-hold) and the experimental curves were fitted by a mechanical model allowing the determination of the time-dependent mechanical properties. Results: Apparent low mineral content impact negatively the mechanical response of bone material at the micro-scale. Mechanical response varies among osteons exhibiting different mineral degrees. The values of the apparent elastic modulus double when the strain rate is analyzed at the extreme values (e=zero and infinity) whatever the bone component. Conclusions: These results evidence the mechanical heterogeneity of bone microstructure due to remodeling process. The quantification of the time-dependent mechanical properties could be useful to improve numerical models of bone behavior and provide new insights to build up original biomimetic materials.