In vitro ultrasonic heating of fetal bone

The temperature increase measured in vitro in human fetal femurs exposed to 1 MHz, continuous wave ultrasound at 37 degrees C is reported. The temperature is measured with a thermocouple probe and is given for several gestational ages. The initial rate of the temperature increase in the specimens is evaluated and compared to known values of absorption in soft tissue. For example, the initial rate of temperature increase in the 108-day gestational age specimen resulting from exposure to ultrasound is 30 times greater in the fetal bone than that of soft tissue with an absorption coefficient of 0.05 cm-1.     

On ultrasound waves guided by bones with coupled soft tissues: A mechanism study and in vitro calibration

The influence of soft tissues coupled with cortical bones on precision of quantitative ultrasound (QUS) has been an issue in the clinical bone assessment in conjunction with the use of ultrasound. In this study, the effect arising from soft tissues on propagation characteristics of guided ultrasound waves in bones was investigated using tubular Sawbones phantoms covered with a layer of mimicked soft tissue of different thicknesses and elastic moduli, and an in vitro porcine femur in terms of the axial transmission measurement. Results revealed that presence of soft tissues can exert significant influence on the propagation of ultrasound waves in bones, leading to reduced propagation velocities and attenuated wave magnitudes compared with the counterparts in a free bone in the absence of soft tissues. However such an effect is not phenomenally dependent on the variations in thickness and elastic modulus of the coupled soft tissues, making it possible to compensate for the coupling effect regardless of the difference in properties of the soft tissues. Based on an in vitro calibration, this study proposed quantitative compensation for the effect of soft tissues on ultrasound waves in bones, facilitating development of high-precision QUS.     

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.     

Wave equations, dispersion relations, and van Hove singularities for applications of doublet mechanics to ultrasound propagation in bio- and nanomaterials

A fundamental mathematical framework for applications of Doublet Mechanics to ultrasound propagation in a discrete material is introduced. A multiscale wave equation, dispersion relation for longitudinal waves, and shear waves are derived. The van Hove singularities and corresponding highest frequency limits for the Mth-order wave equations of longitudinal and shear waves are determined for a widely used microbundle structure. Doublet Mechanics is applied to soft tissue and low-density polyethylene. The experimental dispersion data for soft tissue and low-density polyethylene are compared with results predicted by Doublet Mechanics and an attenuation model based on a Kramers-Kronig relation in classical continuum mechanics.     

Finite-element simulation of ultrasound brain surgery: effects of frequency, focal pressure, and scanning path in bone-heating reduction

In this paper, the finite-element method (FEM) simulation of ultrasound brain surgery is presented. The overheating problem of the post-target bone, which is one of the limiting factors for a successful ultrasound brain surgery, is considered. In order to decrease bone heating, precise choices of frequency, focal pressure, and scanning path are needed. The effect of variations in the mentioned scanning parameters is studied by means of the FEM. The resulting pressure and temperature distributions of a transdural ultrasound brain surgery are simulated by employing the FEM for solving the Helmholtz and bioheat equations in the context of a two-dimensional MRI-based brain model. Our results show that for a suitable value of the frequency, an increase in focal pressure leads to a decrease in the required duration of the treatment and is associated with less heating of the surrounding normal tissue. In addition, it is shown that at a threshold focal pressure, the target temperature reaches toxic levels whereas the temperature rise in the bone is minimal. Wave reflections from sinus cavities, which result in constructive interference with the incoming waves, are one of the reasons for overheating of the bone and can be avoided by choosing a suitable scanning path.      

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.     

Numerical simulation of laser-generated ultrasound in non-metallic material by the finite element method

The use of a pulsed laser for the generation of the elastic waves in non-metallic materials in the thermoelastic regime is investigated by using finite element method (FEM), taking into account not only thermal diffusion and the finite spatial and temporal shape of the laser pulse, but also optical penetration and the temperature dependence of material properties. The optimum finite element model is established based on analysis of two important parameters, meshing size and time step, and the stability of solution. Temperature distributions and temperature gradient fields in non-metallic material for different time steps are obtained, this temperature field is equivalent to a bulk force source to generate ultrasonic wave. The laser-generated ultrasound waveforms at the epicenter and surface acoustic waveforms (SAWs) are obtained and the influence of optical penetration into the material on the temperature field and the ultrasound waveforms are analyzed. The numerical results indicate that the heat penetration into non-metallic material is caused mainly by the optical penetration, and the ultrasound waveforms, especially the shape of the precursor, are strongly dependent on the optical penetration depth into non-metallic material.     

A generalized Westervelt equation for nonlinear medical ultrasound

A model equation is derived for nonlinear medical ultrasound. Unlike the existing models, which use spatial coordinates, material coordinates are used and hence a model for a heterogeneous medium is able to be derived. The equation is a generalization of the Westervelt equation, and includes the nonlinearity, relaxation, and heterogeneity of soft tissue. The validity of the generalized Westervelt equation as a model equation for a Piola-Kirchoff acoustic pressure and as an equation for the acoustic pressure is discussed. In the second case it turns out that the model follows from two geometric approximations which are valid when the radius of curvature of the phase fronts is much larger than the particle displacements. The model is exact for plane waves and includes arbitrary nonlinearity in the stress-strain relation.     

Use of multiple acoustic wave modes for assessment of long bones: model study

Multiple acoustic wave mode method has been proposed as a new modality in axial bone QUS. The new method is based on measurement of ultrasound velocity at different ratio of wavelength to the bone thickness, and taking into account both bulk and guided waves. It allows assessment of changes in both the material properties related to porosity and mineralization as well as the cortical thickness influenced by resorption from inner layers, which are equally important in diagnostics of osteoporosis and other bone osteopenia. Developed method was validated in model studies using a dual-frequency (100 and 500 kHz) ultrasound device. Three types of bone phantoms for long bones were developed and tested: (1) tubular specimens from polymer materials to model combined changes of material stiffness and cortical wall thickness; (2) layered specimens to model porosity in compact bone progressing from endosteum towards periosteum; (3) animal bone specimens with both cortical and trabecular components. Observed changes of the ultrasound velocity of guided waves at 100 kHz followed gradual changes in the thickness of the intact cortical layer. On the other hand, the bulk velocity at 500 kHz remained nearly constant at the different cortical layer thickness but was affected by the material stiffness. Similar trends were observed in phantoms and in fragments of animal bones.     

Intravascular ultrasound elastography: an overview

The composition and morphology of the atherosclerotic lesion are currently considered more important determinants of acute coronary ischemic syndromes than the degree of stenosis. When a lesion is unstable, it may rupture and cause an acute thrombotic reaction. A rupture prone plaque contains a large lipid pool covered by a thin fibrous cap. The stress in the cap increased with decreasing thickness. Additionally, it may be weakened by macrophage infiltration. Intravascular ultrasound elastography might be an ideal technique to assess the presence of lipid pools and identify high stress regions. Elastography is a technique to assess local mechanical properties of tissue. The underlying principle is that the deformation of tissue by a mechanical excitation is a function of its mechanical properties. The deformation of the tissue is determined using ultrasound. For intravascular purposes, the intraluminal pressure is used as the excitation force. The radial strain in the tissue is obtained by cross-correlation techniques on the radio frequency (rf) signal. The strain is colour-coded and plotted as a complimentary image to the IVUS echogram. Elastography was validated in vitro using diseased human coronary and femoral arteries. After the ultrasound experiments, the specimens were processed for routine histology to counterstain collagen, smooth-muscle cells, and macrophage activity. Regions were segmented in the elastograms based on their strain values. Next, the dominant plaque type (fibrous, fibro-fatty or fatty) was defined by observers blinded to the elastographic result. These experiments demonstrate that the strain in the three plaque types is different (Kruskall-Wallis p < 0.001). Especially between fibrous and fatty tissue, a highly significant difference (Wilcoxon p < 0.001) was found. In vivo, the technique is validated in an atherosclerotic Yucatan mini-pig animal model. High-resolution echo frames (30 frames per second) were acquired near end-diastole. In this phase of the pressure cycle, catheter motion was minimal. Frames with a pressure difference of approx. 5 mm Hg were taken to determine the elastograms. This in vivo validation study in Yucatan mini-pigs revealed higher strain values in fatty material (ANOVA p < 0.001). All cross-sections with a fatty plaque were identified with the elastogram by the presence of high strain values. Additionally, data are acquired in patients referred for Percutaneous Transluminal Coronary Angioplasty with the same set-up as tested in the animal study. Ultrasound data of soft, fibrous, calcified and stented plaques are acquired near end-diastole. The elastogram of soft plaques. as identified from the deformation during the pressure cycle, reveals strain values of 1% with increased strain up to 2% at the shoulders of the plaque. Calcified material, as identified from the echogram, shows low strain values of 0-0.2%. The elastogram of stented plaques reveals very low strain values, except for two regions: these are between the stent struts and at the shoulders of the plaque. In conclusion, intravascular elastography appears to be a unique tool to determine local mechanical properties in atherosclerotic lesions to identify fibrous and fatty tissue. Experiments have demonstrated the feasibility of this technique to be applied in vivo.     

Effect of pulse characteristics on temperature rise due to ultrasound absorption at a bone/soft-tissue interface

The transient temperature rise at a bone/soft-tissue interface is an important quantity in the safety evaluation of procedures involving trains of high-intensity ultrasound pulses. Mathematical models based upon the time-averaged intensity of the pulse train can provide rapid estimates of the temperature rise, but are known to underestimate the temperature rise during the on-time of the pulse. This paper extends a previous analytical model to account for pulse shape, and provides error estimates for simulations employing time-averaged intensities. A simple analytic expression for the interface temperature that accounts for both bone and soft-tissue properties is provided. The analytic expression agrees well with temperature rise predictions based upon the finite-element method, when the insonation time is large compared to the pulse repetition period. In this case of large relative insonation time, the pulse shape is found to be inconsequential.     

The effect of boundary conditions on guided wave propagation in two-dimensional models of healing bone

Guided wave propagation has recently drawn significant interest in the ultrasonic characterization of bone. In this work, we present a two-dimensional computational study of ultrasound propagation in healing bones aiming at monitoring the fracture healing process. In particular, we address the effect of fluid loading boundary conditions on the characteristics of guided wave propagation, using both time and time-frequency (t-f) signal analysis techniques, for three study cases. In the first case, the bone was assumed immersed in blood which occupied the semi-infinite spaces of the upper and lower surfaces of the plate. In the second case, the bone model was assumed to have the upper surface loaded by a 2mm thick layer of blood and the lower surface loaded by a semi-infinite fluid with properties close to those of bone marrow. The third case, involves a three-layer model in which the upper surface of the plate was again loaded by a layer of blood, whereas the lower surface was loaded by a 2mm layer of a fluid which simulated bone marrow. The callus tissue was modeled as an inhomogeneous material and fracture healing was simulated as a three-stage process. The results clearly indicate that the application of realistic boundary conditions has a significant effect on the dispersion of guided waves when compared to simplified models in which the bone's surfaces are assumed free.     

Phase velocities and attenuations of shear, Lamb, and Rayleigh waves in plate-like tissues submerged in a fluid (L)

In the past several decades, the fields of ultrasound and magnetic resonance elastography have shown promising results in noninvasive estimates of mechanical properties of soft tissues. These techniques often rely on measuring shear wave velocity due to an external or internal source of force and relating the velocity to viscoelasticity of the tissue. The mathematical relationship between the measured velocity and material properties of the myocardial wall, arteries, and other organs with non-negligible boundary conditions is often complicated and computationally expensive. A simple relationship between the Lamb-Rayleigh dispersion and the shear wave dispersion is derived for both the velocity and attenuation. The relationship shows that the shear wave velocity is around 20% higher than the Lamb-Rayleigh velocity and that the shear wave attenuation is about 20% lower than the Lamb-Rayleigh attenuation. Results of numerical simulations in the frequency range 0-500 Hz are presented.     

Ultrasound elastomicroscopy using water jet and osmosis loading: potentials for assessment for articular cartilage

Research in elasticity imaging typically relies on 1-10 MHz ultrasound. Elasticity imaging at these frequencies can provide strain maps with a resolution in the order of millimeters, but this is not sufficient for applications to skin, articular cartilage, or other fine structures. In this paper, we introduced two methods of ultrasound elastomicroscopy using water jet and osmosis loading for imaging the elasticity of biological soft tissues with high resolutions. In the first system, the specimens were compressed using water jet compression. A water jet was used to couple a focused 20 MHz ultrasound beam into the specimen and meanwhile served as a "soft" indenter. Because there was no additional attenuation when propagating from the ultrasound transducer to the specimen, the ultrasound signal with high signal-to-noise ratio could be collected from the specimens simultaneously with compressing process. The compression was achieved by adjusting the water flow. The pressure measured inside the water pipe and that on the specimen surface was calibrated. This system was easily to apply C-scan over sample surfaces. Experiments on the phantoms showed that this water jet indentation method was reliable to map the tissue stiffness distribution. Results of 1D and 2D scanning on phantoms with different stiffness are reported. In the second system, we used osmotic pressure caused by the ion concentration change in the bathing solutions for the articular cartilage to deform them. When bovine articular cartilage specimens were immerged in solutions with different salt concentration, a 50 MHz focused ultrasound beam was used to monitor the dynamic swelling or shrinkage process. Results showed that the system could reliably map the strain distribution induced by the osmotic loading. We extract intrinsic layered material parameters of the articular cartilage using a triphasic model. In addition to biological tissues, these systems have potential applications for the assessment of bioengineered tissues, biomaterials with fine structures, or some engineering materials. Further studies are necessary to fully realize the potentials of these two new methods.     

Theoretical model of CO2 laser ablation of soft-tissue phantoms

Summary A model of thermal laser ablation of soft tissues is developed taking into consideration two mechanisms: evaporation and liquid moving, due to vapour pressure gradient. Usually a soft tissue is modelled as a single-component material with thermal and optical properties very similar to those of water. We examined the non-stable kinetics of the evaporation process, for short-pulse infrared laser ablation of soft tissues, and we also calculated the average liquid velocity and the ablation rates under vapour pressure gradient. The theoretical results are in good agreement with previous reported experimental data on gelatin and polyacrylamide tissue phantoms The authors of this paper have agreed to not receive the proofs for correction     

Suppression of shocked-bubble expansion due to tissue confinement with application to shock-wave lithotripsy

Estimates are made of the effect of tissue confinement on the response of small bubbles subjected to lithotriptor shock pressures. To do this the Rayleigh-Plesset equation, which governs the dynamics of spherical bubbles, is generalized to treat a bubble in a liquid region (blood), which is in turn encased within an elastic membrane (like a vessel's basement membrane), beyond which a Voigt viscoelastic material models the exterior tissue. Material properties are estimated from a range of measurements available for kidneys and similar soft tissues. Special attention is given to the constitutive modeling of the basement membranes because of their expected importance due to their proximity to the bubble and their toughness. It is found that the highest expected values for the elasticity of the membrane and surrounding tissue are insufficient to suppress bubble growth. The reduced confinement of a cylindrical vessel should not alter this conclusion. Tissue viscosities taken from ultrasound measurements suppress bubble growth somewhat, though not to a degree expected to resist injury. However, the higher reported viscosities measured by other means, which are arguably more relevant to the deformations caused by growing bubbles, do indeed significantly suppress bubble expansion.     

Bulk ablation of soft tissue with intense ultrasound: modeling and experiments

Methods for the bulk ablation of soft tissue using intense ultrasound, with potential applications in the thermal treatment of focal tumors, are presented. An approximate analytic model for bulk ablation predicts the progress of ablation based on tissue properties, spatially averaged ultrasonic heat deposition, and perfusion. The approximate model allows the prediction of threshold acoustic powers required for ablation in vivo as well as the comparison of cases with different starting temperatures and perfusion characteristics, such as typical in vivo and ex vivo experiments. In a full three-dimensional numerical model, heat deposition from array transducers is computed using the Fresnel approximation and heat transfer in tissue is computed by finite differences, accounting for heating changes caused by boiling and thermal dose-dependent absorption. Similar ablation trends due to perfusion effects are predicted by both the simple analytic model and the full numerical model. Comparisons with experimental results show the efficacy of both models in predicting tissue ablation effects. Phenomena illustrated by the simulations and experiments include power thresholds for in vivo ablation, differences between in vivo and ex vivo lesioning for comparable source conditions, the effect of tissue boiling and absorption changes on ablation depth, and the performance of a continuous rotational scanning method suitable for interstitial bulk ablation of soft tissue.     

XRF analysis of strontium: Exploring cellulose as a soft tissue equivalent

X-ray fluorescence (XRF) is a widely used method for in vivo elemental analysis. Particularly for bone, it is a non-invasive technique that provides information on composition without significant risk to the patient. XRF contributes a capability for measuring elements beneficial to human health, such as strontium. This is a proposed supplement that has been shown in clinical trials to reduce fracture risk in people diagnosed with osteoporosis. Although XRF is a viable method for quantifying bone strontium, there are still factors that constrain its effectiveness. X-ray attenuation through overlying soft tissue decreases the signal, consequently requiring correction before estimating the true concentration of strontium in bone. A correction factor can be applied to account for the reduced signal, but an accurate measurement of overlying soft tissue thickness is required. It has been shown that using the correlation between Compton peak count rate and overlying thickness can be used as an estimation of overlying tissue. Lucite is commonly used as a soft tissue substitute; however, its mean atomic number is appreciably lower than soft tissue, somewhat limiting its applicability. This study tests the feasibility of using cellulose filter papers as a substitute for overlying soft tissue to perform XRF analysis of strontium-doped hydroxyapatite bone phantoms. Mass attenuation coefficients are shown to be closer to those of soft tissue (International Commission on Radiation Units' four-component) than Lucite, and the Compton correlation is used to estimate thickness as a correction factor to quantify true strontium concentration.     

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.     

A feasibility study of temperature rise measurement in a tissue phantom as an alternative way for characterization of the therapeutic high intensity focused ultrasonic field

The feasibility that temperature field measurements in vitro as an alternative way to characterize the high intensity focused ultrasound (HIFU) field used in therapeutic applications has been explored in a phantom study. Thermocouples (copper-constantan, diameter 0.125 mm) are embedded in a phantom filled with tissue mimicking material that simulates the thermal and acoustic properties of soft-tissue. The temperature rises as a function of ultrasound exposure time near the focus of a HIFU transducer (1.1 MHz, active radius a = 32 mm, geometric focal length = 62 mm) of various acoustic powers up to 30 W are measured and compared with predicted values using a simple nonlinear Gaussian model. The experimental results can be explained well by the model if no acoustic cavitation takes place. When the acoustic power become higher (>5 W) and the local temperature elevation >15 °C and the local temperature is >40 °C at the focal point, cavitation vapor bubbles appear. The presence of the cavitation bubbles may increase the temperature rise rate initially. The bubble aggregates may form along the beam axis under sonication and then eventually makes the temperature elevation reach a saturated value. When acoustic cavitation occurs, the bubble-assisted enhancement of the initial temperature rise (exposure time t < 2 s) can still be predicted by the theory.