Biomedical subjects

Jeffrey C Bamber

Publications and source records attributed to Jeffrey C Bamber.

12 recordsLinked to original sources

PubMed2006

Coupling between elastic strain and interstitial fluid flow: ramifications for poroelastic imaging.

We study the effects of interstitial fluid flow and interstitial fluid drainage on the spatio-temporal response of soft tissue strain. The motivation stems from the ability to measure in vivo strain distributions in soft tissue via elastography, and the desire to explore the possibility of using such techniques to investigate soft tissue fluid flow. Our study is based upon a mathematical model for soft tissue mechanics from the literature. It is a simple generalization of biphasic theory that includes coupling between the fluid and solid phases of the soft tissue, and crucially, fluid exchange between the interstitium and the local microvasculature. We solve the mathematical equations in two dimensions by the finite element method (FEM). The finite element implementation is validated against an exact analytical solution that is derived in the appendix. Realistic input tissue properties from the literature are used in conjunction with FEM modelling to conduct several computational experiments. The results of these lead to the following conclusions: (i) different hypothetical flow mechanisms lead to different patterns of strain relaxation with time; (ii) representative tissue properties show fluid drainage into the local microvasculature to be the dominant flow-related stress/strain relaxation mechanism; (iii) the relaxation time of strain in solid tumours due to drainage into the microvasculature is on the order of 5-10 s; (iv) under realistic applied pressure magnitudes, the magnitude of the strain relaxation can be as high as approximately 0.4% strain (4000 microstrains), which is well within the range of strains measurable by elastography.

Animals↗

PubMed2006

Spatial and acoustic pressure dependence of microbubble-mediated gene delivery targeted using focused ultrasound.

BACKGROUND: Ultrasound/microbubble-mediated gene delivery has the potential to be targeted to tissue deep in the body by directing the ultrasound beam following vector administration. Application of this technology would be minimally invasive and benefit from the widespread clinical experience of using ultrasound and microbubble contrast agents. In this study we evaluate the targeting ability and spatial distribution of gene delivery using focused ultrasound. METHODS: Using a custom-built exposure tank, Chinese hamster ovary cells in the presence of SonoVue microbubbles and plasmid encoding beta-galactosidase were exposed to ultrasound in the focal plane of a 1 MHz transducer. Gene delivery and cell viability were subsequently assessed. Characterisation of the acoustic field and high-resolution spatial analysis of transfection were used to examine the relationship between gene delivery efficiency and acoustic pressure. RESULTS: In contrast to that seen in the homogeneous field close to the transducer face, gene delivery in the focal plane was concentrated on the ultrasound beam axis. Above a minimum peak-to-peak value of 0.1 MPa, transfection efficiency increased as acoustic pressure increased towards the focus, reaching a maximum above 1 MPa. Delivery was microbubble-dependent and cell viability was maintained. CONCLUSIONS: Gene delivery can be targeted using focused ultrasound and microbubbles. Since delivery is dependent on acoustic pressure, the degree of targeting can be determined by appropriate transducer design to modify the ultrasound field. In contrast to other physical gene delivery approaches, the non-invasive targeting ability of ultrasound makes this technology an attractive option for clinical gene therapy.

Acoustics↗

PubMed2006

Elastography for breast cancer diagnosis using radiation force: system development and performance evaluation.

The use of impulsive acoustic radiation force for strain imaging was investigated. A focused ultrasound transducer was used to apply localized radiation force to a small volume of tissue mimic (100 mm3) for durations of 8 ms. A conventional real-time ultrasound imaging probe was used to obtain echo signals. The resulting strains were mapped using ultrasound correlation-based methods. The instantaneous strain immediately following cessation of the radiation force was observed at depth within homogeneous gels and within stiff inclusions, and was seen to vary approximately linearly with Young's modulus of the material. The highly localized and transient strain that is produced may permit the sensing of variations in tissue elastic properties that are difficult to detect with conventional elastography because of greater independence from boundary conditions. For example, the characteristic, bi-directional, high strain artefacts attributable to stress concentration, often seen with static elastography at tissue-inclusion interfaces, do not appear using the transient radiation force strain imaging technique.

Breast Neoplasms↗

PubMed2006

Towards an acoustic model-based poroelastic imaging method: I. Theoretical foundation.

The ultrasonic measurement and imaging of tissue elasticity is currently under wide investigation and development as a clinical tool for the assessment of a broad range of diseases, but little account in this field has yet been taken of the fact that soft tissue is porous and contains mobile fluid. The ability to squeeze fluid out of tissue may have implications for conventional elasticity imaging, and may present opportunities for new investigative tools. When a homogeneous, isotropic, fluid-saturated poroelastic material with a linearly elastic solid phase and incompressible solid and fluid constituents is subjected to stress, the behaviour of the induced internal strain field is influenced by three material constants: the Young's modulus (E(s)) and Poisson's ratio (nu(s)) of the solid matrix and the permeability (k) of the solid matrix to the pore fluid. New analytical expressions were derived and used to model the time-dependent behaviour of the strain field inside simulated homogeneous cylindrical samples of such a poroelastic material undergoing sustained unconfined compression. A model-based reconstruction technique was developed to produce images of parameters related to the poroelastic material constants (E(s), nu(s), k) from a comparison of the measured and predicted time-dependent spatially varying radial strain. Tests of the method using simulated noisy strain data showed that it is capable of producing three unique parametric images: an image of the Poisson's ratio of the solid matrix, an image of the axial strain (which was not time-dependent subsequent to the application of the compression) and an image representing the product of the aggregate modulus E(s)(1-nu(s))/(1+nu(s))(1-2nu(s)) of the solid matrix and the permeability of the solid matrix to the pore fluid. The analytical expressions were further used to numerically validate a finite element model and to clarify previous work on poroelastography.

Acoustics↗

PubMed2006

Physical parameters affecting ultrasound/microbubble-mediated gene delivery efficiency in vitro.

Ultrasound (US)/microbubble-mediated gene delivery is a technology with many potential advantages suited to clinical application. Previous studies have demonstrated transfection but many are unsatisfactory in respect to the exposure apparatus, lack of definition of the US field or the limitations on parameters that can be explored using clinical diagnostic US machines. We investigated individual exposure parameters using a system minimising experimental artefacts and allowing control of many parameters of the US field. Using a 1-MHz transducer we systematically varied US parameters, the duration of exposure and the microbubble and DNA concentrations to optimise gene delivery. Delivery was achieved, using lipid microbubbles (SonoVue) and clinically acceptable US exposures, to adherent cells at efficiencies of approximately 4%. The acoustic pressure amplitude (0.25 MPa peak-negative), pulse repetition frequency (1-kHz) and duration of exposure (10 s) were important in optimising gene delivery with minimal impact on cell viability. These findings support the hypothesis that varying the physical parameters of US-mediated gene delivery has an affect on both efficiency and cell viability. These data are the first in terms of their thorough exploration of the US parameter space and will be the basis for more-informed approaches to developing clinical applications of this technology.

Animals↗

PubMed2006

Towards an acoustic model-based poroelastic imaging method: II. experimental investigation.

Soft biological tissue contains mobile fluid. The volume fraction of this fluid and the ease with which it may be displaced through the tissue could be of diagnostic significance and may also have consequences for the validity with which strain images can be interpreted according to the traditional idealizations of elastography. In a previous paper, under the assumption of frictionless boundary conditions, the spatio-temporal behavior of the strain field inside a compressed cylindrical poroelastic sample was predicted (Berry et al. 2006). In this current paper, experimental evidence is provided to confirm these predictions. Finite element modeling was first used to extend the previous predictions to allow for the existence of contact friction between the sample and the compressor plates. Elastographic techniques were then applied to image the time-evolution of the strain inside cylindrical samples of tofu (a suitable poroelastic material) during sustained unconfined compression. The observed experimental strain behavior was found to be consistent with the theoretical predictions. In particular, every sample studied confirmed that reduced values of radial strain advance with time from the curved cylindrical surface inwards towards the axis of symmetry. Furthermore, by fitting the predictions of an analytical model to a time sequence of strain images, parametric images of two quantities, each related to one or more of three poroelastic material constants were produced. The two parametric images depicted the Poisson's ratio (nu(s)) of the solid matrix and the product of the aggregate modulus (H(A)) of the solid matrix with the permeability (k) of the solid matrix to the pore fluid. The means of the pixel values in these images, nu(s) = 0.088 (standard deviation 0.023) and H(A)k = 1.449 (standard deviation 0.269) x 10(-7) m(2) s(-1), were in agreement with values derived from previously published data for tofu (Righetti et al. 2005). The results provide the first experimental detection of the fluid-flow-induced characteristic diffusion-like behavior of the strain in a compressed poroelastic material and allow parameters related to the above material constants to be determined. We conclude that it may eventually be possible to use strain data to detect and measure characteristics of diffusely distributed mobile fluid in tissue spaces that are too small to be imaged directly.

Acoustics↗

PubMed2005

Ultrasonic temperature imaging for guiding focused ultrasound surgery: effect of angle between imaging beam and therapy beam.

Ultrasonic temperature imaging is a promising technique for guiding focused ultrasound surgery (FUS). The FUS system is run at an initial, nonablative intensity and a diagnostic transducer images the heat-induced echo strain, which is proportional to the temperature rise. The echo strain image portrays an elliptical "hot spot" corresponding to the focal region of the therapy transducer. It is anticipated that such images will be used to predict the location of the thermal lesion that would be produced at an ablative intensity. We demonstrated in vitro that heat-induced echo strain images can visualize a spatial peak temperature rise of <2 degrees C (starting at room temperature). However, the imaging beam was perpendicular to the treatment beam in these experiments, whereas the most convenient approach in vivo would be to mount the imaging probe within the housing of the therapy transducer such that the two beams are coaxial. A previous simulation experiment predicted that echo strain images would be noisier for the coaxial configuration because sharp lateral gradients in axial displacement cause increased RF signal decorrelation within the beam width. The aim of the current study was to verify this prediction in vitro. We found, that for a temperature rise of approximately 4 degrees C, the mean contrast-to-noise ratio for coaxial and perpendicular echo strain images was 0.37 (+/-0.24) and 2.00 (+/-0.72) respectively. Furthermore, the decorrelation noise seen in the coaxial images obscured the posterior axial border of the hot spot. We conclude that the coaxial configuration will be useful for localizing the hot spot in the lateral direction. However, it may not be able to depict the axial extent of the hot spot or to portray a parameter that is directly related to temperature rise.

Animals↗

PubMed2004

Characterization of cardiovascular liver motion for the eventual application of elasticity imaging to the liver in vivo.

Elastography, which uses ultrasound to image the tissue strain that results from an applied displacement, can display tumours and heat-ablated tissue with high contrast. However, its application to liver in vivo may be problematic due to the presence of respiratory and cardiovascular sources of displacement. The aim of this study was to measure the cardiovascular-induced component of natural liver motion for the purpose of planning future work that will either use the motion to produce elasticity images or will compensate for it when employing an external source of displacement. A total of 36 sequences of 7 s real-time radio frequency (RF) echo images of the liver were acquired from six healthy volunteers during breath-hold using a stationary 3.5 MHz transducer. For each image sequence, the axial and lateral components of displacement were measured for each pair of consecutive RF images using 2D-echo tracking. The spatio-temporal character of these displacements was then analysed using a novel approach, employing proper orthogonal decomposition, whereby the dominant motion patterns are described by eigenvectors with the highest eigenvalues. The motion patterns of different liver segments were complex, but they were also found to be cyclic, highly repeatable and capable of producing measurable displacements in the liver. These observations provide good evidence to suggest that it may be possible to correct for natural liver motion when using an externally applied displacement for elasticity imaging. It was also found that about 65%-70% of all liver motion could be described using the first eigenvector. Use of only this component of the motion will greatly simplify the design of a mechanical system to be used in an objective study of elasticity imaging of phantoms and excised tissues in the presence of simulated cardiovascular-induced liver motion.

Algorithms↗

PubMed2004

Evaluation of the adjoint equation based algorithm for elasticity imaging.

Recently a new adjoint equation based iterative method was proposed for evaluating the spatial distribution of the elastic modulus of tissue based on the knowledge of its displacement field under a deformation. In this method the original problem was reformulated as a minimization problem, and a gradient-based optimization algorithm was used to solve it. Significant computational savings were realized by utilizing the solution of the adjoint elasticity equations in calculating the gradient. In this paper, we examine the performance of this method with regard to measures which we believe will impact its eventual clinical use. In particular, we evaluate its abilities to (1) resolve geometrically the complex regions of elevated stiffness; (2) to handle noise levels inherent in typical instrumentation; and (3) to generate three-dimensional elasticity images. For our tests we utilize both synthetic and experimental displacement data, and consider both qualitative and quantitative measures of performance. We conclude that the method is robust and accurate, and a good candidate for clinical application because of its computational speed and efficiency.

Algorithms↗

PubMed2004

Imaging of temperature-induced echo strain: preliminary in vitro study to assess feasibility for guiding focused ultrasound surgery.

Ultrasonic estimation of heat-induced echo strain has been suggested as a noninvasive technique for guiding focused ultrasound (US) surgery (FUS), that is, for predicting the location of the thermal lesion before it is formed. The proposed strategy is to run the FUS system at a nonablative intensity and to use a diagnostic transducer to image the heat-induced echo strain, which, over a sufficiently small temperature range, is proportional to the temperature rise. The principal aim of this in vitro study was to determine if temperature-induced strain imaging is likely to be able to visualise the small (< 0.5%) strains that one would be restricted to in vivo. Temperature rises ranging from approximately 2 degrees C to 15 degrees C (starting at approximately 25 degrees C) were induced in bovine liver samples using an FUS system. The pre- and post-heated US images were processed to produce images of the apparent axial strain. These images were found to possess excellent spatial and contrast resolution, so that the hot spot remained clearly visible even when the spatial peak strain value was approximately 0.2% (corresponding to temperature rises on the order of 2 to 5 degrees C). Good repeatability in the strain images was observed within and between tissue samples. Artefacts due to thermoacoustic refraction were seen distal to the heated region, but they did not reduce hot spot visibility. The length of the hot spot exceeded that of the subsequent ablation (by approximately 200%), which was to be expected given that temperature imaging depicts the entire area over which the temperature has increased relative to the baseline. We conclude that temperature-induced strain imaging for the guidance of FUS in the liver is likely to be feasible, provided that it will be possible either to neglect or to correct for the additional sources of error (such as cardiac-induced motion) that will arise in vivo.

Acoustics↗

PubMed2002

Quantitative elasticity imaging: what can and cannot be inferred from strain images.

We examine the inverse problem associated with quantitative elastic modulus imaging: given the equilibrium strain field in a 2D incompressible elastic material, determine the elastic stiffness (shear modulus). We show analytically that a direct formulation of the inverse problem has no unique solution unless stiffness information is known a priori on a sufficient portion of the boundary. This implies that relative stiffness images constructed on the assumption of constant boundary stiffness are in error, unless the stiffness is truly constant on the boundary. We show further that using displacement boundary conditions in the forward incompressible elasticity problem leads to a nonunique inverse problem. Indeed, we give examples in which exactly the same strain field results from different elastic modulus distributions under displacement boundary conditions. We also show that knowing the stress on the boundary can, in certain configurations, lead to a well-posed inverse problem for the elastic stiffness. These results indicate what data must be taken if the elastic modulus is to be reconstructed reliably and quantitatively from a strain image.

Computer Simulation↗

PubMed2002

Fundamental limitations of noninvasive temperature imaging by means of ultrasound echo strain estimation.

Ultrasonic estimation of temperature-induced echo strain has been suggested as a means of predicting the location of thermal lesions formed by focused ultrasound (US) surgery before treatment. Preliminary investigations of this technique have produced optimistic results because they were carried out with rubber phantoms and used room temperature, rather than body temperature, as the baseline. The objective of the present study was to determine, through modelling, the likely feasibility of using ultrasonic temperature imaging to detect and localise the focal region of the heating beam for a medium with a realistic temperature-dependence of sound speed subjected to a realistic temperature rise. We determined the minimum ultrasonic signal-to-noise ratio (SNR) required to visualise the heated region for liver of varying fat content. Due to the small (0.5%) change in sound speed at the focus, the threshold SNR for normal liver (low fat content) was found to be at least 20 dB. This implies that temperature imaging in this tissue type will only be feasible if the effects of electronic noise can be minimised and if other sources of noise, such as cardiac-induced motion, do not substantially reduce the visibility of the focal region. For liver of intermediate fat content, the heated region could not be visualised even when the echo data were noise-free. Tissues with a very high fat content are likely to represent the most favourable conditions for ultrasonic temperature imaging.

Body Temperature↗