Tissue Elasticity

Dynamic optical coherence elastography (OCE) tracks elastic wave propagation speed within tissue, enabling quantitative three-dimensional imaging of the elastic modulus. We show that propagating mechanical waves are mode converted at interfaces, creating a finite region on the order of an acoustic wavelength where there is not a simple one-to-one correspondence between wave speed and elastic modulus. Depending on the details of a boundary's geometry and elasticity contrast, highly complex propagating fields produced near the boundary can substantially affect both the spatial resolution and contrast of the elasticity image. We demonstrate boundary effects on Rayleigh waves incident on a vertical boundary between media of different shear moduli. Lateral resolution is defined by the width of the transition zone between two media and is the limit at which a physical inclusion can be detected with full contrast. We experimentally demonstrate results using a spectraldomain OCT system on tissue-mimicking phantoms, which are replicated using numerical simulations. It is shown that the spatial resolution in dynamic OCE is determined by the temporal and spatial characteristics (i.e., bandwidth and spatial pulse width) of the propagating mechanical wave. Thus, mechanical resolution in dynamic OCE inherently differs from the optical resolution of the OCT imaging system.

The material properties of the trabeculae (tissue-level properties), together with the trabecular architecture and the bone volume fraction determine the apparent millimetre-scale bone mechanical properties. We present a novel method to measure trabecular tissue elastic modulus E t using resonant ultrasound spectroscopy (RUS). The first mechanical resonance frequency f e of a freestanding

Low trauma fractures are amongst the most frequently encountered problems in the clinical assessment and treatment of bones, with dramatic health consequences for individuals and high financial costs for health systems. Consequently, significant research efforts have been dedicated to the development of accurate computational models of bone biomechanics and strength. However, the estimation of the fabric tensors, which describe the microarchitecture of the bone, has proven to be challenging using in vivo imaging. On the other hand, existing research has shown that isotropic models do not produce accurate predictions of stress states within the bone, as the the material properties of the trabecular bone are anisotropic. In this paper, we present the first biomechanical study that uses statistically-derived fabric tensors for the estimation of bone strength in order to obtain patient-specific results. We integrate a statistical predictive model of trabecular bone microarchitecture previously constructed from a sample of ex vivo micro-CT datasets within a biomechanical simulation workflow. We assess the accuracy and flexibility of the statistical approach by estimating fracture load for two different databases and bone sites, i.e., for the femur and the T12 vertebra. The results obtained demonstrate good agreement between the statistically-driven and micro-CT-based estimates, with concordance coefficients of 98.6% and 95.5% for the femur and vertebra datasets, respectively.

As in clinical studies, finite element analysis (FEA) developed from computed tomography (CT) images of bones are useful in pre-clinical rodent studies assessing treatment effects on vertebral body (VB) strength. Since strength predictions from microCT-derived FEAs (mFEA) have not been validated against experimental measurements of mouse VB strength, a parametric analysis exploring material and failure definitions was performed to determine whether elastic mFEAs with linear failure criteria could reasonably assess VB strength in two studies, treatment and genetic, with differences in bone volume fraction between the control and the experimental groups. VBs were scanned with a 12-mm voxel size, and voxels were directly converted to 8-node, hexahedral elements. The coefficient of determination or R 2 between predicted VB strength and experimental VB strength, as determined from compression tests, was 62.3% for the treatment study and 85.3% for the genetic study when using a homogenous tissue modulus (E t) of 18 GPa for all elements, a failure volume of 2%, and an equivalent failure strain of 0.007. The difference between prediction and measurement (that is, error) increased when lowering the failure volume to 0.1% or increasing it to 4%. Using inhomogeneous tissue density-specific moduli improved the R 2 between predicted and experimental strength when compared with uniform E t ¼ 18 GPa. Also, the optimum failure volume is higher for the inhomogeneous than for the homogeneous material definition. Regardless of model assumptions, mFEA can assess differences in murine VB strength between experimental groups when the expected difference in strength is at least 20%.

While in clinical settings, bone mineral density measured by computed tomography (CT) remains the key indicator for bone fracture risk, there is an ongoing quest for more engineering mechanics-based approaches for safety analyses of the skeleton. This calls for determination of suitable material properties from respective CT data, where the traditional approach consists of regression analyses between attenuation-related grey values and mechanical properties. We here present a physics-oriented approach, considering that elasticity and strength of bone tissue originate from the material microstructure and the mechanical properties of its elementary components. Firstly, we reconstruct the linear relation between the clinically accessible grey values making up a CT, and the Xray attenuation coefficients quantifying the intensity losses from which the image is actually reconstructed. Therefore, we combine X-ray attenuation averaging at different length scales and over different tissues, with recently identified 'universal' composition characteristics of the latter. This gives access to both the normally non-disclosed X-ray energy employed in the CT-device and to in vivo patient-specific and location-specific bone composition variables, such as voxel-specific mass density, as well as collagen and mineral contents. The latter feed an experimentally validated multiscale elastoplastic model based on the hierarchical organization of bone. Corresponding elasticity maps across the organ enter a finite element simulation of a typical load case, and the resulting stress states are increased in a proportional fashion, so as to check the safety against ultimate material failure. In the young patient investigated, even normal physiological loading is probable to already imply plastic events associated with the hydrated mineral crystals in the bone ultrastructure, while the safety factor against failure is still as high as five.

Following previous studies employing X-ray physics and continuum micromechanics in order to retrieve voxel-specific elastic properties from Computed Tomographs (CT) (Hellmich et al., 2008), we here present an updated and improved approach applied to in-vivo images of vertebrae of a young patient. This approach concerns both elasticity and strength, and therefore promises considerable impact on patient-individual, image-based fracture risk assessment. This is done for the described voxel-specific heterogeneous case, as well as for vascular porosities averaged over the trabecular core. Homogeneous simulations obviously underestimate the fracture risk in the presently studies case

Synopsis The Gas Bearing Electrodynamometer (GBE)(1) has been used for the last 20 years to obtain sensitive measurements of the stratum corneum. A new instrument for measuring the mechanical properties of the stratum corneum incorporates all of the measurement principles of the GBE but none of its components. A force-controlled miniature dc servo, gearing and leadscrew replace the magnet/solenoid arrangement of the GBE. Error resulting from conversion of an electrical signal to a mechanical force is ...

Intra-voxel micro-elasto-plasticity for CT-based patient-specific fracture risk assessment of vertebrae Romane Blanchard1, Claire Morin, Alain Vella3, Zdenka Sant3, and Christian Hellmich1 1 Vienna University of Technology, Institute for Mechanics of Materials and Structures, Karlsplatz 13/202, A-1040 Vienna, Austria 2 Ecole Nationale Supérieure des Mines, CIS-EMSE, CNRS:UMRS146, LGF, F-42023, Saint-Etienne, France 3 University of Malta, Mechanical Engineering Department, Tal Qroqq, Msida MSD 2080, Malta

The recently developed Reference Point Indentation (RPI) allows the measurements of bone properties at the tissue level in vivo. The goal of this study was to compare the local anisotropic behaviour of bovine plexiform bone measured with depth sensing micro-indentation tests and with RPI. Fifteen plexiform bone specimens were extracted from a bovine femur and polished down to 0.05 mm alumina paste for indentations along the axial, radial and circumferential directions (N¼5 per group). Twenty-four micro-indentations (2.5 mm in depth, 10% of them were excluded for testing problems) and four RPI-indentations ($ 50 mm in depth) were performed on each sample. The local indentation modulus E ind was found to be highest for the axial direction (24.372.5 GPa) compared to the one for the circumferential indentations (19% less stiff) and for the radial direction (30% less stiff). RPI measurements were also found to be dependent on indentation direction (po0.001) with the exception of the Indentation Distance Increase (IDI) (p¼0.173). In particular, the unloading slope US1 followed similar trends compared to the E ind : 0.4770.03 N/mm for axial, 11% lower for circumferential and 17% lower for radial. Significant correlations were found between US1 and E ind (p¼ 0.001; R 2 ¼0.58), while no significant relationship was found between IDI and any of the micro-indentation measurements (p40.157). In conclusion some of the RPI measurements can provide information about local anisotropy but IDI cannot. Moreover, there is a linear relationship between most local mechanical properties measured with RPI and with micro-indentations, but IDI does not correlate with any micro-indentation measurements.

For cortical bone, important changes of the elastic properties values have been clearly shown in ageing but not in childhood, furthermore recent works considered osteoporosis as a pediatric disease with geriatric consequences and children are concerned by specific infantile osteo-pathologies. That is why there is a strong interest in the characterisation of the growing process of children bone. However, few mechanical properties of cortical growing bone are available in literature and do not yield to gold standards. Results found in litterature for children bone concern specific location (close to cancerous cells) or cadaveric bone. They indicate a lower Young's modulus for children bone compare to mature bone. The goal of this study is to provide elastic properties values for human growing cortical bone. To reach this goal, we have analysed surgery waste (bone transplantation) from long bone (fibula). In a first step, a non destructive method was used to evaluate the velocity of ultrasonic waves from which the acoustic Young's modulus E a is calculated using the difference of sound path duration and the mass density. Then, in a second step, a destructive method was used to obtain mechanical Young's modulus E m using a 3-point microbending. Heihteen children bone samples were tested acoustically and due to the specific dimensions needed for micro three points bending fourteen samples were tested this way, but for each step, comparisons were made with adult specimens (twelve samples). The children surgery wastes from fibula (4 to 16 year old children) included in this study show an average E a and ν a of 15.5 GPa (+/-3.4) and 0.24 (+/-0.08) at 10 MHz , and an average E m of 9.1 GPa (+/-3.5). E a and ν a are in the same range for children and seniors but a linear correlation between E a and E m is found only for the fourteen samples of the children group.

Urinary incontinence (UI) is a distressing condition involving involuntary loss of urine from the body. Urinary incontinence can negatively impact a person's overall quality of life and lead them into stages of embarrassment and depression. It is an underrepresented and undertreated condition prevalent in women, especially in low socioeconomic regions where women may not be able to express their concerns due to unawareness of diagnosis and treatment/management options. There are different diagnostic and management protocols for UI; however, utilizing artificially intelligent systems is not standard care. This paper overviews the use of artificial intelligence in women's health and as a means of cost-effectively diagnosing patients, and as an avenue for providing low-cost treatments to women that suffer from urinary incontinence in low-resource communities. Studies found that these systems, mainly utilizing artificial neural networks (ANNs) and convolutional neural networks (CNNs), served to be an effective method in diagnosing patients and providing an avenue for personalized treatment for improved patient outcomes. A simple artificial intelligence (AI) model utilizing Multilayer Perceptron (MLP) Networks was proposed to diagnose and manage urinary incontinence.

The elastic moduli of trabecular bone were modeled using an analytical multiscale approach. Trabecular bone was represented as a porous nanocomposite material with a hierarchical structure spanning from the collagen-mineral level to the trabecular architecture level. In parallel, compression testing was done on bovine femoral trabecular bone samples in two anatomical directions, parallel to the femoral neck axis and perpendicular to it, and the measured elastic moduli were compared with the corresponding theoretical results. To gain insights on the interaction of collagen and minerals at the nanoscale, bone samples were deproteinized or demineralized. After such processing, the treated samples remained as self-standing structures and were tested in compression. Micro-computed tomography was used to characterize the hierarchical structure of these three bone types and to quantify the amount of bone porosity. The obtained experimental data served as inputs to the multiscale model and guided us to represent bone as an interpenetrating composite material. Good agreement was found between the theory and experiments for the elastic moduli of the untreated, deproteinized, and demineralized trabecular bone.

The reference point indentation (RPI) method is a microindentation technique involving successive indentation cycles. We employed RPI to measure average stiffness (Ave US), indentation distance increase (IDI), total indentation distance (TID), average energy dissipated (Ave ED), and creep indentation distance (CID) of swine femoral cortical bone (mid-diaphysis) as a function of age (1, 3.5, 6, 14.5, 24, and 48 months) and loading directions (longitudinal and transverse). The Ave US increases with animal age, while the IDI, TID, Ave ED, and CID decrease with age, for both longitudinal (transverse surface) and transverse (periosteal surface) loading directions. Longitudinal measurements generally give higher Ave US and lower IDI and TID values compared to transverse measurements. The RPI measurements show similar trends to those obtained using nanoindentation test, and ash and water content tests.

The extremely fine structure of vertebral cortex challenges reliable determination of the tissue's anisotropic elasticity, which is important for the spine's load carrying patterns often causing pain in patients. As a potential remedy, we here propose a combined experimental (ultrasonic) and modeling (micromechanics) approach. Longitudinal acoustic waves are sent in longitudinal (superior-inferior, axial) as well as transverse (circumferential) direction through millimeter-sized samples containing this vertebral cortex, and corresponding wave velocities agree very well with recently identified 'universal' compositional and acoustic characteristics (J Theor Biol 287:115, 2011), which are valid for a large data base comprising different bones from different species and different organs. This provides evidence that the 'universal' organization patterns inherent to all the bone tissues of the aforementioned data base also hold for vertebral bone. Consequently, an experimentally validated model covering the mechanical effects of this organization patterns (J Theor Biol 244:597, 2007, J Theor Biol 260:230, 2009) gives access to the complete elasticity tensor of human lumbar vertebral bone tissue, as a valuable input for structural analyses aiming at patient-specific fracture risk assessment, e.g. based on the Finite Element Method.

Hundred micrometers-sized porous hydroxyapatite globules have proved as a successful tissue engineering strategy for bone defects in vivo, as was shown in studies on human mandibles. These granules need to provide enough porous space for bone ingrowth, while maintaining sufficient mechanical competence (stiffness and strength) in this highly load-bearing organ. This double challenge motivates us to scrutinize more deeply the micro-and nanomechanical characteristics of such globules, as to identify possible optimization routes. Therefore, we imaged such a (pre-cracked) granule in a microCT scanner, transformed the attenuation coefficients into voxel-specific nanoporosities, from which we determined, via polycrystal micromechanics, voxel-specific (heterogeneous) elastic properties. The importance of the latter and of the presence of one to several hundred micrometers-sized cracks for realistically estimating the load-carrying behavior of the globule under a typical two-point compressive loading (as in a ''splitting'' test) is shown through results of large-scale Finite Element analyses, in comparison to analytical results for a sphere loaded at its poles: Use of homogeneous instead of heterogeneous elastic properties would overestimate the structure's stiffness by 5% (when employing a micromechanics-based process as to attain homogeneous properties)-the cracks, in comparison, weaken the structure by one to two orders of magnitudes.

Centrifugal microfluidics, as a field of microfluidics, has shown impressive improvements in manufacturing of the medical systems implementing biological diagnostic methods such as immunoassay and polymerase chain reaction (PCR) assay. PCR is a powerful method for amplification of the DNA samples utilizing cycling through three specific temperatures. This paper presents a numerical analysis for the simulation of the thermocycling process in a disc-based microfluidic cartridge. The simulated model consists of a liquid chamber located into a rotating disc and a heating unit for raising the temperature of embedded liquid. Disc spin frequency and heating element position are two major parameters that can affect the temperature distribution in the disc and liquid regions whose influences are determined. Thermal profiles of the liquid are presented applying appropriate initial and boundary conditions. The results indicate the more influence of the distance of heating element from the disc compare with the rotation frequency of the disc.

ABSIXACT Osteoporotic frartures follow a period of asymptomatic bone loss and hence bone strength, predominantly in cancellous bone. An effective management of osteoporosis require,? an understanding of the mechaniral behauiour of cnncelhs bone including the anisotropic dependence. Ultraso~und velority (V) and elasticity (Young's modulus, E) awe mearured in the three orIhogona1 dirertions in 20 mm cubes of bovine cancellous bone. Student paired t-test analysis showed si~gnz$cant variations in velot-ity and elasticity for the three orthogonal directions, the highest s@zifirance bping between proximal-distal (PD) and an&&posterior (At') directions with t = 5.63 and 4.09 for velocity and elasticity respectively, the lowest significance between mediolateral (ML) and anter@flostpn'or dirertions. Elastirity Jollowed a power law relationship with appawnt density (p) as reported in the literature, the exponent (b) being direction dependent (b = 1.98 + 0.2 1 for PD, 2.42 + 0.24 for AP and 2.03 z!z 0.17 Jtir ML). The adjusted R' va1ue.T between elasticity and apparent density were highly signijcant (79.9% for PD, 81.9% Jar AP and 85.7% Jor ML). The relationship between velocity and apparent density is less signzjirant in terms of the amount ofvariance explained (483% for PD, 63.3% for AP and 64.4% for ML). R" values relating elasticity and velocity were again high!? signifirant (79.4% ,for PD, 82.9% for AP an.d 80.5y/o for ML) and the roej$cients, determined 67 reCgre.Gin analysis, independent oJ direction. Analysis of velocity. rlastirity and density data for a range oJref&renre materials demonstrated that experimentally measured long-itudinal wave velocity could be reliably substituted into the bar wave equation (v = mp) This imp&T that a combination of velocity and apparent density may be an improved indicator oJbonr fkg+lit? than density alone.

The Gas Bearing Electrodynamometer (GBE)(1) has been used for the last 20 years to obtain sensitive measurements of the stratum corneum. A new instrument for measuring the mechanical properties of the stratum corneum incorporates all of the measurement principles of the GBE but none of its components. A force-controlled miniature d.c. servo, gearing and leadscrew replace the magnet / solenoid arrangement of the GBE. Error resulting from conversion of an electrical signal to a mechanical force is automatically compensated. Consequently, this control renders the need for a friction-free bearing redundant. The original Linear Variable Differential Transformer (LVDT) has been replaced with a unit with a sensitivity of 0.01% and force is now measured by a calibrated 50g load beam. The function generator, signal conditioner and storage oscilloscope have been replaced by user-friendly software run by a small portable computer. The new design offers greater inherent accuracy than the GBE and requires minimal servicing. The new instrument (Linear Skin Rheometer, "LSR" ) has been shown to provide sensitive measurements of stratum corneum mechanics and was used to measure the mechanical responses of the stratum corneum to two topical moisturising treatments of differing relative hydration performance (as determined by impedance measurements using the Nova™ DPM9003). The relative performance of the two products as measured by the LSR compared favourably with corresponding impedance data, indicating the ability of the LSR to differentiate varying degrees of stratum corneum plasticisation in response to hydration.

The extremely fine structure of vertebral cortex challenges reliable determination of the tissue's anisotropic elasticity, which is important for the spine's load carrying patterns often causing pain in patients. As a potential remedy, we here propose a combined experimental (ultrasonic) and modeling (micromechanics) approach. Longitudinal acoustic waves are sent in longitudinal (superior-inferior, axial) as well as transverse (circumferential) direction through millimeter-sized samples containing this vertebral cortex, and corresponding wave velocities agree very well with recently identified ‘universal’ compositional and acoustic characteristics (J Theor Biol 287:115, 2011), which are valid for a large data base comprising different bones from different species and different organs. This provides evidence that the ‘universal’ organization patterns inherent to all the bone tissues of the aforementioned data base also hold for vertebral bone. Consequently, an experimentally validated model covering the mechanical effects of this organization patterns (J Theor Biol 244:597, 2007, J Theor Biol 260:230, 2009) gives access to the complete elasticity tensor of human lumbar vertebral bone tissue, as a valuable input for structural analyses aiming at patient-specific fracture risk assessment, e.g. based on the Finite Element Method.