Ultrasonically determined thickness of long cortical bones: two-dimensional simulations of in vitro experiments

Previously it has been demonstrated that cortical bone thickness can be estimated from ultrasonic guided-wave measurements, in an axial transmission configuration, together with an appropriate analytical model. This study considers the impact of bone thickness variation within the measurement region on the ultrasonically determined thickness (UTh). To this end, wave velocities and UTh were determined from experiments and from time-domain finite-difference simulations of wave propagation, both performed on a set of ten human radius specimens (29 measurement sites). A two-dimensional numerical bone model was developed with tunable material properties and individualized geometry based on x-ray computed-tomography reconstructions of human radius. Cortical thickness (CTh) was determined from the latter. UTh data for simulations were indeed in a excellent accordance (root-mean-square error was 0.26 mm; r2=0.94, p<0.001) with average CTh within the measurement region. These results indicate that despite variations in cortical thickness along the propagation path, the measured phase velocity can be satisfactorily modeled by a simple analytical model (the A(0) plate mode in this case). Most of the variability (up to 85% when sites were carefully matched) observed in the in vitro ultrasound data was explained through simulations by variability in the cortical thickness alone.     

Numerical simulation of the dependence of quantitative ultrasonic parameters on trabecular bone microarchitecture and elastic constants

Finite-difference numerical simulation of ultrasound propagation in complex media such as cancellous bone represents a fertile alternative to analytical approaches because it can manage the complex 3D bone structure by coupling the numerical computation with 3D numerical models of bone microarchitecture obtained from high-resolution imaging modalities. The objective of this work was to assess in silico the sensitivity of ultrasound parameters to controlled changes of microarchitecture and variation of elastic constants. The simulation software uses a finite-difference approach based on the Virieux numerical scheme. An incident plane wave was propagated through a volume of bone of approximately 5 x 5 x 8 mm(3). The volumes were reconstructed from high-resolution micro-computed tomography data. An iterative numerical scenario of "virtual osteoporosis" was implemented using a dedicated image processing algorithm in order to modify the initial 3D microstructures. Numerical computations of wave propagation were performed at each step of the process. The sensitivity to bone material properties was also tested by changing the elastic constants of bone tissue. Our results suggest that ultrasonic variables (slope of the frequency-dependent attenuation coefficient and speed of sound) are mostly influenced by bone volume fraction. However, material properties and structure also appear to play a role. The impact of modifications of the stiffness coefficients remained lower than the variability caused by structural variations. This study emphasizes the potential of numerical computations tools coupled to realistic 3D structures to elucidate the physical mechanisms of interaction between ultrasound and bone structure and to assess the sensitivity of ultrasound variables to different bone properties.     

Feasibility of bone assessment with leaky Lamb waves in bone phantoms and a bovine tibia

In this study, the effect of cortical thickness variation on the propagation of leaky Lamb waves is investigated by using an axial transmission technique commonly used to characterize long bones. Three Lucite plates with thicknesses of 1, 3, and 5 mm as bone phantoms and one bovine tibia with a cortical thickness of 2 mm were used at various low frequencies. Experimental measurements in bone phantoms show that the peak frequency and amplitude of excited Lamb modes strongly depend on the thickness of the Lucite plate. In the bovine tibia, the S0 and A0 Lamb modes are consistently observed in the frequency-thickness region from 0.2 to 1.0 MHz mm, and can be effectively launched at a frequency of 200 kHz, suggesting 200 kHz to be the optimal signal frequency for in vivo clinical applications. It can be also seen that both modes are affected by the frequency-thickness product, but the effect is greater for the A0 mode. Hence, the A0 Lamb mode seems more sensitive to cortical thickness change due to aging and osteoporosis. This study suggests that the use of leaky Lamb waves is feasible for ultrasonic bone assessment.     

Peri-implant osteogenesis in health and osteoporosis

Long-term clinical success of endosseous dental implants is critically related to a wide bone-to-implant direct contact. This condition is called osseointegration and is achieved ensuring a mechanical primary stability to the implant immediately after implantation. Both primary stability and osseointegration are favoured by micro-rough implant surfaces which are obtained by different techniques from titanium implants or coating the titanium with different materials. Host bone drilled cavity is comparable to a common bone wound. In the early bone response to the implant, the first tissue which comes into contact with the implant surface is the blood clot, with particular attention to platelets and fibrin. Peri-implant tissue healing starts with an inflammatory response as the implant is inserted in the bone cavity, but an early afibrillar calcified layer comparable to the lamina limitans or incremental lines in bone is just observable at the implant surface both in vitro than in vivo conditions. Just within the first day from implantation, mesenchymal cells, pre-osteoblasts and osteoblasts adhere to the implant surface covered by the afibrillar calcified layer to produce collagen fibrils of osteoid tissue. Within few days from implantation a woven bone and then a reparative trabecular bone with bone trabeculae delimiting large marrow spaces rich in blood vessels and mesenchymal cells are present at the gap between the implant and the host bone. The peri-implant osteogenesis can proceed from the host bone to the implant surface (distant osteogenesis) and from the implant surface to the host bone (contact osteogenesis) in the so called de novo bone formation. This early bone response to the implant gradually develops into a biological fixation of the device and consists in an early deposition of a newly formed reparative bone just in direct contact with the implant surface. Nowadays, senile and post-menopausal osteoporosis are extremely diffuse in the population and have important consequences on the clinical success of endosseous dental implants. In particular the systemic methabolic and site morphological conditions are not favorable to primary stability, biological fixation and final osseointegration.

An early good biological fixation may allow the shortening of time before loading the implant, favouring the clinical procedure of early or immediate implant loading. Trabecular bone in implant biological fixation is gradually substituted by a mature lamellar bone which characterizes the implant ossoeintegration. As a final consideration, the mature lamellar bone observed in osseointegrated implants is not always the same as a biological turnover occurs in the peri-implant bone up to 1 mm from the implant surface, with both osteogenesis and bone reabsorption processes.     

Ultrasonically determined thickness of long cortical bones: Three-dimensional simulations of in vitro experiments

It was reported in a previous study that simulated guided wave axial transmission velocities on two-dimensional (2D) numerically reproduced geometry of long bones predicted moderately real in vitro ultrasound data on the same bone samples. It was also shown that fitting of ultrasound velocity with simple analytical model yielded a precise estimate (UTh) for true cortical bone thickness. This current study expands the 2D bone model into three dimensions (3D). To this end, wave velocities and UTh were determined from experiments and from time-domain finite-difference simulations of wave propagation, both performed on a collection of 10 human radii (29 measurement sites). A 3D numerical bone model was developed with tuneable fixed material properties and individualized geometry based on X-ray computed tomography reconstructions of real bones. Simulated UTh data were in good accordance (root-mean-square error was 0.40 mm; r(2)=0.79, p<0.001) with true cortical thickness, and hence the measured phase velocity can be well estimated by using a simple analytical inversion model also in 3D. Prediction of in vitro data was improved significantly (by 10% units) and the upgraded bone model thus explained most of the variability (up to 95% when sites were carefully matched) observed in in vitro ultrasound data.     

Ultrasonic non-destructive measurements of cortical bone thickness in human cadaver femur

The knowledge of the cortical bone thickness profile in human bone has a two-fold clinical significance: to study the stress occurring in a loaded bone structure to optimize the design of prostheses; and to predict the onset of advanced bone disease such as osteoporosis. In this study, the cortical bone thickness in three embalmed human cadaver femora were measured non-destructively using an ultrasonic technique. These thickness measurements were also made using a computed tomographic (CT) scanning method. Subsequently bones were sectioned and the actual bone thicknesses in the same regions were measured using a micrometer. The correlation coefficient between the actual thickness and the ultrasonically measured thickness was 0.95 and with the CT was 0.62. Thus, these results show that, under present experimental conditions, ultrasonic thickness measurements compare well with the micrometer actual thickness results. This technique, when fully developed, can be used as a non-destructive tool for quantitative cortical bone thickness measurements. Moreover, the ultrasonic technique does not use ionizing radiation.     

Advances in the ultrastructural study of the implant-bone interface by backscattered electron imaging

The biocompatibility of titanium implants in bone depends on the response shown by cells in contact with the implant surface. Several developments have been targeted at achieving successful implant treatment. The aim of this study was to develop a novel preparation procedure to evaluate the bone cell response produced at the bone–implant interface using the technique scanning electron microscopy with backscattered electron imaging (SEM-BSE). Dental prostheses with an SLA-modified or TOP-modified surface were implanted in a toothless part of the mandibula in female pigs. The animals were sacrificed 12 weeks after surgery, at which time block specimens containing the implants were obtained. These specimens were then processed for SEM-BSE by optimizing a protocol involving chemical fixation and heavy metal staining. In addition, element distribution maps for the implant–bone tissue interface were obtained using a microanalytical system based on energy-dispersive X-ray spectrometry (EDS). This novel visualisation approach enabled a comprehensive study of the extracellular matrix and cell components of the host tissues neoformed around the implant. SEM-BSE images also provided ultrastructural details of the bone cells. This technique appears to be an effective and very promising tool for detailed studies on the implant–bone tissue interface and the host response to the bone incorporation process.     

Bio-activated titanium surface utilizable for mimetic bone implantation in dentistry—Part III: Surface characteristics and bone–implant contact formation

This study was carried out to quantify the effect of an alkali-modified surface on the bone–implant interface formation during healing using an animal model. A total of 24 screw-shaped, self-tapping, (c.p.) titanium dental implants, divided into test group B—implants with alkali-modified surface (Bio surface) and control group M—implants with turned, machined surface, were inserted without pre-tapping in the tibiae of three beagle dogs. The animals were sacrificed after 2, 5 and 12 weeks and the bone–implant contact (BIC%) was evaluated histometrically. The surface characteristics that differed between the implant surfaces, i.e. specific surface area, contact angle, may represent factors that influence the rate of osseointegration and the secondary implant stability. The alkali-treated surface enhances the BIC formation during the first 2–5 weeks of healing compared to the turned, machined surface.     

Application of an effective medium theory for modeling ultrasound wave propagation in healing long bones

Quantitative ultrasound has recently drawn significant interest in the monitoring of the bone healing process. Several research groups have studied ultrasound propagation in healing bones numerically, assuming callus to be a homogeneous and isotropic medium, thus neglecting the multiple scattering phenomena that occur due to the porous nature of callus. In this study, we model ultrasound wave propagation in healing long bones using an iterative effective medium approximation (IEMA), which has been shown to be significantly accurate for highly concentrated elastic mixtures. First, the effectiveness of IEMA in bone characterization is examined: (a) by comparing the theoretical phase velocities with experimental measurements in cancellous bone mimicking phantoms, and (b) by simulating wave propagation in complex healing bone geometries by using IEMA. The original material properties of cortical bone and callus were derived using serial scanning acoustic microscopy (SAM) images from previous animal studies. Guided wave analysis is performed for different healing stages and the results clearly indicate that IEMA predictions could provide supplementary information for bone assessment during the healing process. This methodology could potentially be applied in numerical studies dealing with wave propagation in composite media such as healing or osteoporotic bones in order to reduce the simulation time and simplify the study of complicated geometries with a significant porous nature.     

Multi-frequency axial transmission bone ultrasonometer

The last decade has seen a surge in the development of axial transmission QUS (Quantitative UltraSound) technologies for the assessment of long bones using various modes of acoustic waves. The condition of cortical bones and the development of osteoporosis are determined by numerous mechanical, micro-structural, and geometrical or macro-structural bone properties like hardness, porosity and cortical thickness. Such complex manifestations of osteoporosis require the evaluation of multiple parameters with different sensitivities to the various properties of bone that are affected by the disease. This objective may be achieved by using a multi-frequency ultrasonic examination The ratio of the acoustic wavelength to the cortical thickness can be changed by varying the frequency of the ultrasonic pulse propagating through the long bone that results in the change in composition of the induced wave comprised of a set of numerous modes of guided, longitudinal, and surface acoustic waves. The multi-frequency axial transmission QUS method developed at Artann Laboratories (Trenton, NJ) is implemented in the Bone Ultrasonic Scanner (BUSS). In the current version of the BUSS, a train of ultrasonic pulses with 60, 100, 400, 800, and 1200 kHz frequencies is used. The developed technology was tested on a variety of bone phantoms simulating normal, osteopenic, and osteoporotic bones. The results of this study confirm the feasibility of the multi-frequency approach for the assessment of the processes leading to osteoporosis.     

A hybrid FDTD-Rayleigh integral computational method for the simulation of the ultrasound measurement of proximal femur

The development of novel quantitative ultrasound (QUS) techniques to measure the hip is critically dependent on the possibility to simulate the ultrasound propagation. One specificity of hip QUS is that ultrasounds propagate through a large thickness of soft tissue, which can be modeled by a homogeneous fluid in a first approach. Finite difference time domain (FDTD) algorithms have been widely used to simulate QUS measurements but they are not adapted to simulate ultrasonic propagation over long distances in homogeneous media. In this paper, an hybrid numerical method is presented to simulate hip QUS measurements. A two-dimensional FDTD simulation in the vicinity of the bone is coupled to the semi-analytic calculation of the Rayleigh integral to compute the wave propagation between the probe and the bone. The method is used to simulate a setup dedicated to the measurement of circumferential guided waves in the cortical compartment of the femoral neck. The proposed approach is validated by comparison with a full FDTD simulation and with an experiment on a bone phantom. For a realistic QUS configuration, the computation time is estimated to be sixty times less with the hybrid method than with a full FDTD approach.     

Biological and physical properties of pulsed-Laser-deposited zirconia/hydroxyapatite on titanium: In vitro study

Coating dental implants with hydroxyapatite (HA) may give certain advantages such as active encouragement of new bone growth, a lower rejection rate, and an improved long-term prosthesis fixation. This study examined the mechanical and biological properties of titanium alloy implant cores with an interlayer of zirconia and a coating of HA created using pulsed Laser deposition (PLD). The thickness of the zirconia layer was 50–100 nm, and the HA layer was ～600 nm. The crystallinity, morphology, wettability, and Ca/P ratio of the HA layer were investigated by electron microscopy, X-ray diffraction, goniometric measurement of contact angle, and wavelength dispersive X-ray analysis. The physical tests indicated adequate mechanical properties and a satisfactory adhesion to a titanium core modified with zirconia and HA. Cell proliferation and metabolic activity of human embryonal lung fibroblasts were determined using counting of harvested cells and providing an MTT assay. it was demonstrated that none of the samples were cytotoxic and their surfaces promoted cell colonization. PLD was found to be a promising method of applying coatings to a metal core for dental implants, and the in vitro biological tests suggest that the crystalline HA coating can improve the biological properties of titanium covered with zirconia.     

Studies by imaging TOF-SIMS of bone mineralization on porous titanium implants after 1 week in bone

Anodic oxidation was used to grow porous layers on titanium discs. Six different oxidation procedures were used producing six different surfaces. The implants were inserted in rat bone (tibia) for 7 days. After implant retrieval, mineralization (hydroxyapatite formation) on the implant surfaces was investigated using time-of-flight secondary ion mass spectrometry (TOF-SIMS). Bone tissue around the implants was sectioned and stained. The amount of bone in close apposition to the implant was calculated. The porosity showed great variation between the surfaces. Hydroxyapatite was detected on all surfaces. A slight positive correlation between porosity and mineralization was found, although the most porous surface was not the best mineralized one. Bone had formed around all implants after 7 days. The bone-to-metal contact for the porous implants did not differ significantly from the non-porous control. Porosity is known to influence cellular events. The results indicate that porosity could have an initial, positive influence on bone integration of implants, by stimulating the mineralization process. The methods used were found to be suitable tools for investigation of initial healing around implants in bone.     

A Wavelet-Based Processing method for simultaneously determining ultrasonic velocity and material thickness

Methods of measuring ultrasonic wave velocity in an elastic sample require data on the thickness of the sample and/or the distances between the transducers and the sample. The uncertainty of the ultrasonic wave velocity measurements generally depends on that of the data available. Conversely, to determine the thickness of a material, it is necessary to have a priori information about the wave velocity. This problem is particularly hard to solve when measuring the parameters of biological specimens such as bones having a greater acoustical impedance contrast (typically 3-5 MRayl) than that of the surrounding soft tissues (typically 1.5 MRayl). Measurements of this kind cannot easily be performed. But obtaining the thickness of a bone structure and/or the ultrasonic wave velocity is a important problem, for example, in biomechanical field for the calculation of elastic modulus, or in acoustical imaging field to parameterize the images, and to reference the grey or color level set to a physical parameter.The aim of the present study was to develop a method of simultaneously and independently determining the velocity of an ultrasonic wave in an elastic sample and the wave path across the thickness of this sample, using only one acquisition in pure transmission mode. The new method, which we have called the “Wavelet-Based Processing” method, is based on the wavelet decomposition of the signals and on a suitable transmitted incident wave correlated with the experimental device, and the mathematical properties such as orthonormality, of which lend themselves well to the time-scale approach. By following an adapted algorithm, ultrasonic wave velocities in parallelepipedic plates of elastic manufactured material and the apparent thicknesses were both measured using a water tank, a mechanical device and a matched pair of 1 MHz ultrasonic focused transducers having a diameter of 3 mm, a focal length of 150 mm and beam width of 2 × 2 mm at the focus (mean temperature 22°). The results were compared with those obtained with a conventional Pulse-mode method and with the control values, to check their validity. Measurements performed on bovine and human dry cortical bone samples are also presented to assess the limitations of the method when it is applied to elastic biological samples, including those of an equal-wavelength size (≈1.5 mm). The thicknesses and the ultrasonic wave velocities were then measured in this kind of (quasi-) parallelepipedic elastic materials with an mean estimated error ranged from 1% to 3.5% compared to the referenced values.     

Effects of an implant on temperature distribution in tissue during ultrasound diathermy

The effects of an implant on temperature distribution in a tissue-mimicking hydrogel phantom during the application of therapeutic ultrasound were investigated. In vitro experiments were conducted to compare the influences of plastic and metal implants on ultrasound diathermy and to calibrate parameters in finite element simulation models. The temperature histories and characteristics of the opaque (denatured) areas in the hydrogel phantoms predicted by the numerical simulations show good correlation with those observed in the in vitro experiments. This study provides an insight into the temperature profile in the vicinity of an implant by therapeutic ultrasound heating typically used for physiotherapy. A parametric study was conducted through numerical simulations to investigate the effects of several factors, such as implant material type, ultrasound operation frequency, implant thickness and tissue thickness on the temperature distribution in the hydrogel phantom. The results indicate that the implant material type and implant thickness are the main parameters influencing the temperature distribution. In addition, once the implant material and ultrasound operation frequency are chosen, an optimal implant thickness can be obtained so as to avoid overheating injuries in tissue.     

骨小梁材料特性对超声背散射信号的影响

基于时域有限差分法(FDTD)建立了松质骨的超声背散射仿真系统,研究了骨小梁材料特性对超声背散射信号的影响。首次得到松质骨中的超声背散射系数(BSC)和积分背散射系数(IBC)随骨小梁材料参数(密度、拉梅常数、黏度系数及声阻抗系数)的变化关系。研究结果表明,IBC随骨小梁密度的增加而增加;BSC和IBC随拉梅常数的增加而增加、随第一黏度系数的增加而近似线性地减小,第二黏度的变化对背散射信号的影响很小;背散射参数随阻抗系数的增加而减小。说明松质骨中的超声背散射特性不仅受骨矿密度(BMD)和骨微结构的影响,还与骨小梁的材料参数密切相关。研究结果有利于理解松质骨中超声的背散射特性,对松质骨骨质状况的评价有一定帮助。      

The dual-frequency method for ultrasonic assessment of skeletal system

The article is a review of the new dual-frequency method in axial bone quantitative ultrasonometry for assessment of changes in cortical bones in osteoporosis. The method is based on the use of two frequencies for the generation of flexural and longitudinal ultrasonic waves, which opens possibilities for differential diagnostics of changes in various components of the state of the skeletal system, such as cortical layer thickness, porosity, and elastic properties of tissue. The axial scanning and composition of two-dimensional acoustic profiles of bones are carried out with the purpose of using topographic variations in the acoustic properties for diagnostics of the state of a bone. Results of laboratory and clinical tests of Bone UltraSonic Scanner (BUSS) developed in Artann Laboratories on the basis of the stated principles are presented. The sensitivity of measured characteristics to progression of osteoporosis and the detectability of early changes in bones related to this disease are shown.

     

Effect of porosity on effective diagonal stiffness coefficients (cii) and elastic anisotropy of cortical bone at 1 MHz: a finite-difference time domain study

Finite-difference time domain (FDTD) numerical simulations coupled to real experimental data were used to investigate the propagation of 1 MHz pure bulk wave propagation through models of cortical bone microstructures. Bone microstructures were reconstructed from three-dimensional high resolution synchrotron radiation microcomputed tomography (SR-muCT) data sets. Because the bone matrix elastic properties were incompletely documented, several assumptions were made. Four built-in bone matrix models characterized by four different anisotropy ratios but the same Poisson's ratios were tested. Combining them with the reconstructed microstructures in the FDTD computations, effective stiffness coefficients were derived from simulated bulk-wave velocity measurements. For all the models, all the effective compression and shear bulk wave velocities were found to decrease when porosity increases. However, the trend was weaker in the axial direction compared to the transverse directions, contributing to the increase of the effective anisotropy. On the other hand, it was shown that the initial Poisson's ratio value may substantially affect the variations of the effective stiffness coefficients. The present study can be used to elaborate sophisticated macroscopic computational bone models incorporating realistic CT-based macroscopic bone structures and effective elastic properties derived from muCT-based FDTD simulations including the cortical porosity effect.     

超声轴向传播技术评价长骨的研究

用超声轴向传播技术评价长骨状况已成为近年来的一个研究热点。本文首先介绍了第一到达波(FAS)法、超声Lamb波及柱面导波法在评价长骨皮质骨状况方面的研究进展,最后分析和讨论了当前研究中存在的问题及应该研究的方向。