Coupled field analysis of heat flow in the near field of a microwave applicator for tumor ablation

Microwave tumor ablation (MTA) offers a new approach for the treatment of hepatic neoplastic disease. Reliable and accurate information regarding the heat distribution inside biological tissue subjected to microwave thermal ablation is important for the efficient design of microwave applicators and for optimizing experiments, which aim to assess the effects of therapeutic treatments. Currently there are a variety of computational methods based on different vascular structures in tissue, which aim to model heat distribution during ablation. This paper presents results obtained from two such computational models for temperature distributions produced by a clinical 2.45 GHz MTA applicator immersed in unperfused ex vivo bovine liver, and compares them with measured results from a corresponding ex vivo experiment. The computational methods used to model the temperature distribution in tissue caused by the insertion of a 5.6 mm diameter "wandlike" microwave applicator are the Green's function method and the finite element method (FEM), both of which provide solutions of the heat diffusion partial differential equation. The results obtained from the coupled field simulations are shown to be in good agreement with a simplified analysis based on the bio-heat equation and with ex vivo measurements of the heat distribution produced by the clinical MTA applicator.     

An isolated rat liver model for the evaluation of thermal techniques to quantify perfusion

An isolated, thermally regulated, perfused rat liver model system is presented. The model was developed to evaluate thermal methods to quantify perfusion in small volumes of tissue. The surgically isolated rat liver is perfused with an isothermal oxygenated Krebs-Ringer bicarbonate buffer solution via the cannulated portal vein. A constant-pressure head variable-resistance scheme is utilized to control the total flow to the liver. Total flow is quantified by hepatic vein collection. The spatial distribution of perfusion within the liver is determined using two independent methods. In the first method, radio-labelled microspheres are injected into the portal vein, and the regional flow distribution is determined from the relative radioactivity of each section of tissue. In the second method, the tissue is thermally perturbed, and the time constant of the tissue temperature recovery is measured. The regional distribution is determined from the relative time constants of each section of tissue. Both methods require the measurement of total liver flow to determine the absolute perfusion at each point. Results obtained by the two methods were well correlated (0.973). The rat liver system offers a stable, controllable, and measurable perfusion model for the evaluation of new perfusion measurement techniques.     

Finite element modelling of radial shock wave therapy for chronic plantar fasciitis

Therapeutic use of high-amplitude pressure waves, or shock wave therapy (SWT), is emerging as a popular method for treating musculoskeletal disorders. However, the mechanism(s) through which this technique promotes healing are unclear. Finite element models of a shock wave source and the foot were constructed to gain a better understanding of the mechanical stimuli that SWT produces in the context of plantar fasciitis treatment. The model of the shock wave source was based on the geometry of an actual radial shock wave device, in which pressure waves are generated through the collision of two metallic objects: a projectile and an applicator. The foot model was based on the geometry reconstructed from magnetic resonance images of a volunteer and it comprised bones, cartilage, soft tissue, plantar fascia, and Achilles tendon. Dynamic simulations were conducted of a single and of two successive shock wave pulses administered to the foot. The collision between the projectile and the applicator resulted in a stress wave in the applicator. This wave was transmitted into the soft tissue in the form of compression–rarefaction pressure waves with an amplitude of the order of several MPa. The negative pressure at the plantar fascia reached values of over 1.5 MPa, which could be sufficient to generate cavitation in the tissue. The results also show that multiple shock wave pulses may have a cumulative effect in terms of strain energy accumulation in the foot.     

Identifying a minimal rheological configuration: a tool for effective and efficient constitutive modeling of soft tissues

We describe a modeling methodology intended as a preliminary step in the identification of appropriate constitutive frameworks for the time-dependent response of biological tissues. The modeling approach comprises a customizable rheological network of viscous and elastic elements governed by user-defined 1D constitutive relationships. The model parameters are identified by iterative nonlinear optimization, minimizing the error between experimental and model-predicted structural (load-displacement) tissue response under a specific mode of deformation. We demonstrate the use of this methodology by determining the minimal rheological arrangement, constitutive relationships, and model parameters for the structural response of various soft tissues, including ex vivo perfused porcine liver in indentation, ex vivo porcine brain cortical tissue in indentation, and ex vivo human cervical tissue in unconfined compression. Our results indicate that the identified rheological configurations provide good agreement with experimental data, including multiple constant strain rate load/unload tests and stress relaxation tests. Our experience suggests that the described modeling framework is an efficient tool for exploring a wide array of constitutive relationships and rheological arrangements, which can subsequently serve as a basis for 3D constitutive model development and finite-element implementations. The proposed approach can also be employed as a self-contained tool to obtain simplified 1D phenomenological models of the structural response of biological tissue to single-axis manipulations for applications in haptic technologies.     

Method and apparatus for soft tissue material parameter estimation using tissue tagged Magnetic Resonance Imaging

We describe an experimental method and apparatus for the estimation of constitutive parameters of soft tissue using Magnetic Resonance Imaging (MRI), in particular for the estimation of passive myocardial material properties. MRI tissue tagged images were acquired with simultaneous pressure recordings, while the tissue was cyclically deformed using a custom built reciprocating pump actuator A continuous three-dimensional (3D) displacement field was reconstructed from the imaged tag motion. Cavity volume changes and local tissue microstructure were determined from phase contrast velocity and diffusion tensor MR images, respectively. The Finite Element Method (FEM) was used to solve the finite elasticity problem and obtain the displacement field that satisfied the applied boundary conditions and a given set of material parameters. The material parameters which best fit the FEM predicted displacements to the displacements reconstructed from the tagged images were found by nonlinear optimization. The equipment and method were validated using inflation of a deformable silicon gel phantom in the shape of a cylindrical annulus. The silicon gel was well described by a neo-Hookian material law with a single material parameter C1=8.71+/-0.06kPa, estimated independently using a rotational shear apparatus. The MRI derived parameter was allowed to vary regionally and was estimated as C1 =8.80+/-0.86kPa across the model. Preliminary results from the passive inflation of an isolated arrested pig heart are also presented, demonstrating the feasibility of the apparatus and method for isolated heart preparations. FEM based models can therefore estimate constitutive parameters accurately and reliably from MRI tagging data.     

间质热疗法组织中温度分布与光纤加入端的关系

主要利用了有限元方法,模拟研究了在激光间质热疗法中,被加热区域组织中温度的分布情况。组织的温度对组织中细胞有着极其重要的影响,对温度的控制是间质热疗法成败的关键因素。到目前为止,在激光间质热疗法中,还没有一种很精确方法能够实时测量激光辐射后组织中温度分布。为了能为临床处理提供一些有用参考,利用Ansys对不同的光纤加入端所形成的温度场进行了模拟,不失为一种好的方法。     

Patient-specific finite element model of the spine and spinal cord to assess the neurological impact of scoliosis correction: preliminary application on two cases with and without intraoperative neurological complications

Scoliosis is a 3D deformation of the spine and rib cage. For severe cases, surgery with spine instrumentation is required to restore a balanced spine curvature. This surgical procedure may represent a neurological risk for the patient, especially during corrective maneuvers. This study aimed to computationally simulate the surgical instrumentation maneuvers on a patient-specific biomechanical model of the spine and spinal cord to assess and predict potential damage to the spinal cord and spinal nerves. A detailed finite element model (FEM) of the spine and spinal cord of a healthy subject was used as reference geometry. The FEM was personalized to the geometry of the patient using a 3D biplanar radiographic reconstruction technique and 3D dual kriging. Step by step surgical instrumentation maneuvers were simulated in order to assess the neurological risk associated to each maneuver. The surgical simulation methodology implemented was divided into two parts. First, a global multi-body simulation was used to extract the 3D displacement of six vertebral landmarks, which were then introduced as boundary conditions into the personalized FEM in order to reproduce the surgical procedure. The results of the FEM simulation for two cases were compared to published values on spinal cord neurological functional threshold. The efficiency of the reported method was checked considering one patient with neurological complications detected during surgery and one control patient. This comparison study showed that the patient-specific hybrid model reproduced successfully the biomechanics of neurological injury during scoliosis correction maneuvers.     

3D-finite element analyses of cusp movements in a human upper premolar, restored with adhesive resin-based composites

The combination of diverse materials and complex geometry makes stress distribution analysis in teeth very complicated. Simulation in a computerized model might enable a study of the simultaneous interaction of the many variables. A 3D solid model of a human maxillary premolar was prepared and exported into a 3D-finite element model (FEM). Additionally, a generic class II MOD cavity preparation and restoration was simulated in the FEM model by a proper choice of the mesh volumes. A validation procedure of the FEM model was executed based on a comparison of theoretical calculations and experimental data. Different rigidities were assigned to the adhesive system and restorative materials. Two different stress conditions were simulated: (a) stresses arising from the polymerization shrinkage and (b) stresses resulting from shrinkage stress in combination with vertical occlusal loading. Three different cases were analyzed: a sound tooth, a tooth with a class II MOD cavity, adhesively restored with a high (25 GPa) and one with a low (12.5GPa) elastic modulus composite. The cusp movements induced by polymerization stress and (over)-functional occlusal loading were evaluated. While cusp displacement was higher for the more rigid composites due to the pre-stressing from polymerization shrinkage, cusp movements turned out to be lower for the more flexible composites in case the restored tooth which was stressed by the occlusal loading.This preliminary study by 3D FEA on adhesively restored teeth with a class II MOD cavity indicated that Young's modulus values of the restorative materials play an essential role in the success of the restoration. Premature failure due to stresses arising from polymerization shrinkage and occlusal loading can be prevented by proper selection and combination of materials.     

Radiobiological aspects of intraoperative radiotherapy (IORT) with isotropic low-energy X rays for early-stage breast cancer

The purpose of this study was to model the distribution of biological effect around a miniature isotropic X-ray source incorporating spherical applicators for single-dose or hypo-fractionated partial-breast intraoperative radiotherapy. A modification of the linear-quadratic formalism was used to calculate the relative biological effectiveness (RBE) of 50 kV X rays as a function of dose and irradiation time for late-reacting normal tissue and tumor cells. The response was modeled as a function of distance in the tissue based on the distribution of equivalent dose and published dose-response data for pneumonitis and subcutaneous fibrosis after single-dose conventional irradiation. Furthermore, the spatial distribution of tumor cell inactivation was assessed. The RBE for late reactions approached unity at the applicator surface but increased as the absorbed dose decreased with increasing distance from the applicator surface. The ED50 for pneumonitis was estimated to be reached at a depth of 6-11 mm in the tissue and that for subcutaneous fibrosis at 3-6 mm, depending on the applicator diameter and whether the effect of recovery was included. Thus lung tissue would be spared because of the thickness of the thorax wall. The RBE for tumor cells was higher than for late-reacting tissue. The applicator diameter is an important parameter in determining the range of tumor cell control in the irradiated tumor bed.     

Perfused phantom models of microwave irradiated tissue

The theoretical basis, practical design considerations, and prototype testing of a perfused model suitable for simulation studies of microwave heated tissue are presented. A parallel tube heat exchanger configuration is used to simulate the internal convection effects of blood flow. The global thermal response of the phantom, on a scale of several tube spacings, is shown theoretically to be nearly identical to that predicted by Pennes' bioheat equation, which is known to give a reasonable representation of tissue under many conditions. A parametric study is provided for the relationships between the tube size, spacing and material properties and the simulated perfusion rate. A prototype with a physiologically reasonable perfusion rate was tested using a typical hyperthermia applicator. The measured thermal response of the phantom compares favorably with the numerical solution of the bioheat equation under the same irradiation conditions. This similarity sheds light on the unexpected success of the bioheat equation for modeling the thermal response of real tissue.     

Assessment of ideal neutron beams for neutron capture therapy.

The discrete-ordinates transport computer code DORT has been used to develop a two-dimensional cylindrical phantom model for use as a tool to assess beam design and dose distributions for boron neutron capture therapy. The model uses an S8 approximation for angular fluxes and a P3 Legendre approximation for scattering cross sections. A one-dimensional discrete-ordinates model utilizing the computer code ANISN was used to validate the energy-group structure used in the two-dimensional calculations. In the two-dimensional model the effects of varying basic parameters such as aperture width, neutron source energy, and tissue composition have been studied. Identical results were obtained when comparing narrow beam calculations to fine-mesh higher-order Sn treatments (up to S32), and with P5 cross sections. It is shown that, when the correct assessment volume is used, narrow beams will give little or no advantage for therapy even with an optimum-energy ideal neutron beam.     

Light- and electron-microscopic study of the rat esophagus following intraluminal argon laser irradiation

36 rat esophagi were irradiated by argon laser via an applicator with circumferential light distribution. They were perfused with glutaraldehyde and studied by light and transmission electron microscopy immediately, 2 days and 14 days after irradiation. Immediately after irradiation the laser center showed destruction of the keratinized stratified squamous epithelium. The collagenous fibers of the connective tissue were altered; fibrocytes and fibroblasts were severely damaged, and the microvascular lumina were occluded. The smooth muscle tissue and skeletal muscle tissue showed myofilament defects and initial karyonecrosis. There was decreasing damage of both fiber types up to 4 mm from the laser center. After 2 days the morphology of the laser center was not different from that seen immediately after irradiation. At a distance of 2 mm a partly differentiated new epithelium emerged below the necrotic epithelium. An inflammatory reaction was found in the connective tissue. After 14 days the esophageal wall was replaced and the lumen was occluded by young granulation tissue in the former laser center. Peripherally the esophageal wall appeared almost normal. As the rat esophagus serves as a model for esophagotracheal fistulae in newborn children, our findings indicate that the argon laser should be capable of occluding these fistulae likewise.     

The isolated perfused rabbit ovary — A model for studies of ovarian function

Summary In the present investigation the ultrastructure of isolated rabbit ovaries, perfused with different media for various time periods, was studied. The steroid hormone production by the perfused ovary was also determined. Perfusion with Medium 199 results in prominent interstitial ovarian oedema which increases with perfusion time. Even after the addition of 6–10 % Dextran T40, oedema appears in the interstitial tissue of the ovary. Perfusion solutions with osmotically active colloid particles of large molecular size (Dextran T70; average molecular weight 70,000 and bovine serum albumin), cause less distortion in the ovarian structure, and ultrastructurally the ovarian tissues appear essentially the same as in the control ovaries.The results indicate that the perfused rabbit ovary, under strictly controlled conditions, can be used as an experimental model for studies of various aspects of ovarian function, including follicular rupture.     

Finite-element-analysis and experimental investigation in a femur with hip endoprosthesis

The stress distribution in a human femur with an endoprosthesis was determined. The finite element method (FEM) was used for a three-dimensional model with more than 15000 degrees of freedom. Geometrical and material data had been taken for this model from a left femur with endoprosthesis. On the contralateral bone a strain gauge investigation was performed to validate the calculations. Reasonable agreement was achieved. Various modes of loading were investigated. A perfect bond at the interface between materials of different elastic moduli was assumed. The results are valid for endoprosthesis with such structured stem surfaces as allow transfer of tensile and shear stresses.     

Perfusion bioreactor-based cryopreservation of 3D human mesenchymal stromal cell tissue grafts

The generation of an off-the-shelf in vitro engineered living tissue graft will likely require cryopreservation. However, the efficient addition and removal of cryoprotective agents (CPA) to cells throughout the volume of a three-dimensional (3D) tissue graft remains a significant challenge. In this work, we assessed whether a perfusion bioreactor-based method could be used to improve the viability of cryopreserved mesenchymal stromal cell- (MSC) based tissue constructs as compared to using conventional diffusion-based methods. The bioreactor was first used to saturate 3D constructs with CPA under perfused flow. Following cryopreservation, the bioreactor was then also used for the efficient removal of the CPA from the 3D tissues. We demonstrate that addition and removal of CPA under perfused flow significantly increased the viability of MSC within cryopreserved 3D tissue constructs as compared to conventional diffusion-based methods.     

Calculation of electric fields induced in the human knee by a coil applicator

Calculations are presented of the induced electric fields and current densities in the cartilage of the knee produced by a coil applicator developed for applying pulsed magnetic fields to osteoarthritic knees. This applicator produces a sawtooth-like magnetic field waveform composed of a series of 260-micros pulses with a peak to peak magnitude of approximately 0.12 mT in the cartilage region. The simulations were performed using a recently developed 3 dimensional finite difference frequency domain technique for solving Maxwell's equations with an equivalent circuit model. The tissue model was obtained from the anatomically segmented human body model of Gandhi. The temporal peak electric field magnitude was found to be -153 mV/m, averaged within the medial cartilage of the knee for the typical dB/dt excitation levels of this coil. The technique can be extended to analyze other excitation waveforms and applicator designs.     

Validation of a commercial TPS based on the VMC++ Monte Carlo code for electron beams: Commissioning and dosimetric comparison with EGSnrc in homogeneous and heterogeneous phantoms

The aim of the present work was the validation of the VMC⁺⁺ Monte Carlo (MC) engine implemented in the Oncentra Masterplan (OMTPS) and used to calculate the dose distribution produced by the electron beams (energy 5-12 MeV) generated by the linear accelerator (linac) Primus (Siemens), shaped by a digital variable applicator (DEVA). The BEAMnrc/DOSXYZnrc (EGSnrc package) MC model of the linac head was used as a benchmark.Commissioning results for both MC codes were evaluated by means of 1D Gamma Analysis (2%, 2 mm), calculated with a home-made Matlab (The MathWorks) program, comparing the calculations with the measured profiles. The results of the commissioning of OMTPS were good [average gamma index (γ) > 97%]; some mismatches were found with large beams (size ≥ 15 cm). The optimization of the BEAMnrc model required to increase the beam exit window to match the calculated and measured profiles (final average γ > 98%).Then OMTPS dose distribution maps were compared with DOSXYZnrc with a 2D Gamma Analysis (3%, 3 mm), in 3 virtual water phantoms: (a) with an air step, (b) with an air insert, and (c) with a bone insert.The OMTPD and EGSnrc dose distributions with the air-water step phantom were in very high agreement (γ ∼ 99%), while for heterogeneous phantoms there were differences of about 9% in the air insert and of about 10–15% in the bone region. This is due to the Masterplan implementation of VMC⁺⁺ which reports the dose as “dose to water”, instead of “dose to medium”.     

Modeling the electromobility of ions in a target tissue

Electroporation is a clinical and laboratory technique for the delivery of molecules to cells. This method imposes electric fields onto cells or tissues through the use of electrodes and a set of electrical parameters to ultimately incorporate molecules into the cells. Clinical applications may include using directional fields to bring therapeutics to the target tissues before triggering an electroporation event. The choice of applicator may also have a significant influence on this molecular flow. Modeling ionic flow in tissues will yield insight into selecting the appropriate parameters or electroporation signature for a desired target application. In this paper, the motion of tissue injected ions was modeled for two common electroporation applicator configurations-the parallel plate, and the four needle electrodes. This electric field induced fluid flow model predicts that the parallel plate applicator ultimately directs the movement of an ionic therapeutic in a forward manner with side motion due only to obstruction, while the four-needle applicator directs anisotropic flow within the field ultimately forcing the therapeutic into a mound at the fringes of the induced electric field.     

Determination of microvessel permeability and tissue diffusion coefficient of solutes by laser scanning confocal microscopy

Interstitium contains a matrix of fibrous molecules that creates considerable resistance to water and solutes in series with the microvessel wall. On the basis of our preliminary studies, by using laser-scanning confocal microscopy and a theoretical model for interstitial transport, we determined both microvessel solute permeability (P) and solute tissue diffusion coefficient (D) of alpha-lactalbumin (Stokes radius 2.01 nm) from the rate of tissue solute accumulation and the radial concentration gradient around individually perfused microvessel in frog mesentery. P(alpha-lactalbumin) is 1.7 +/- 0.7(SD) x 10(-6) cm/s (n = 6). D(t)/D(free) for alpha-lactalbumin is 27% +/- 5% (SD) (n = 6). This value of D(t)/D(free) is comparable to that for small solute sodium fluorescein (Stokes radius 0.45 nm), while p(alpha-lactalbumin) is only 3.4% of p(sodium fluorescein). Our results suggest that frog mesenteric tissue is much less selective to solutes than the microvessel wall.     

Perfusion cultures and modelling of oxygen uptake with three-dimensional chondrocyte pellets

Chondrocyte pellets were cultivated in a perfused flow chamber and supplied with medium by a constant flow rate from a conditioning vessel. In this conditioning vessel the medium was aerated and used medium was exchanged semi-continuously. The higher amount of DNA and glycosaminoglycane (GAG) in these pellets compared to control cultures under stationary conditions showed a positive effect of the reactor system, compared to standard culture conditions. A diffusion reaction model was applied to calculate the oxygen uptake of the cell pellet and to describe the oxygen profile within the pellet. The model included diffusion within the cell pellet and oxygen uptake of the cells. Calculated data were compared to experimental data obtained by tissue engineered chondrocyte cell pellets. Model calculations agreed rather well with experimental data.