Tissue-mimicking Phantom Materials Research Articles

Experimental observations of Scholte waves propagating in an incompressible soft solid

Due to the heterogeneous structure of the soft biological tissue, such as the brain, surface waves might be important to elucidate the biomechanics of injury formation from impacts. In this context, surface waves generate a wavelength on the order of the centimeter with a typical penetration length of the same order. Therefore, investigating surface waves at depth is crucial for understanding their relationship with the physics of soft tissue injuries. Planar surface waves produce particle motion along two dimensions, the direction of propagation and the depth direction, making them more challenging to measure when compared to polarized shear waves that only produce motion in one direction. This study presents an experimental setup capable of generating Scholte wave propagating in a soft solid–liquid interface. In particular, we studied a tissue-mimicking phantom material, such as gelatin, under a layer of water. Ultrasound imaging techniques, operating at 8600 frames per second, and a one-dimensional cross-correlation algorithm were used to independently estimate the two components of the wave’s particle displacement. We conducted experiments sweeping frequencies between 50 and 500 Hz for different gelatin stiffness, finding a surface wave speed of 0.86 times the shear wave speed and a penetration distance of 0.35 times the wavelength. These results agree with the theory of Scholte waves propagating in an incompressible semi-infinite elastic medium covered by an incompressible fluid.

Tissue-mimicking phantom materials with tunable optical properties suitable for assessment of diffuse reflectance spectroscopy during electrosurgery.

Emerging intraoperative tumor margin assessment techniques require the development of more complex and reliable organ phantoms to assess the performance of the technique before its translation into the clinic. In this work, electrically conductive tissue-mimicking materials (TMMs) based on fat, water and agar/gelatin were produced with tunable optical properties. The composition of the phantoms allowed for the assessment of tumor margins using diffuse reflectance spectroscopy, as the fat/water ratio served as a discriminating factor between the healthy and malignant tissue. Moreover, the possibility of using polyvinyl alcohol (PVA) or transglutaminase in combination with fat, water and gelatin for developing TMMs was studied. The diffuse spectral response of the developed phantom materials had a good match with the spectral response of porcine muscle and adipose tissue, as well as in vitro human breast tissue. Using the developed recipe, anatomically relevant heterogeneous breast phantoms representing the optical properties of different layers of the human breast were fabricated using 3D-printed molds. These TMMs can be used for further development of phantoms applicable for simulating the realistic breast conserving surgery workflow in order to evaluate the intraoperative optical-based tumor margin assessment techniques during electrosurgery.

Acoustic characterization of tissue-mimicking materials for ultrasound perfusion imaging research.

Materials with well-characterized acoustic properties are of great interest for the development of tissue-mimicking phantoms with designed (micro)vasculature networks. These represent a useful means for controlled in-vitro experiments to validate perfusion imaging methods such as Doppler and contrast-enhanced ultrasound (CEUS) imaging. In this work, acoustic properties of seven tissue-mimicking phantom materials at different concentrations of their compounds and five phantom case materials are characterized and compared at room temperature. The goal of this research is to determine the most suitable phantom and case material for ultrasound perfusion imaging experiments. The measurements show a wide range in speed of sound varying from 1057 to 1616 m/s, acoustic impedance varying from 1.09 to 1.71×106 kg/m2s, and attenuation coefficients varying from 0.1 to 22.18 dB/cm at frequencies varying from 1 MHz to 6 MHz for different phantom materials. The nonlinearity parameter B/A varies from 6.1 to 12.3 for most phantom materials. This work also reports the speed of sound, acoustic impedance and attenuation coefficient for case materials. According to our results, polyacrylamide (PAA) and polymethylpentene (TPX) are the optimal materials for phantoms and their cases, respectively. To demonstrate the performance of the optimal materials, we performed power Doppler ultrasound imaging of a perfusable phantom, and CEUS imaging of that phantom and a perfusion system. The obtained results can assist researchers in the selection of the most suited materials for in-vitro studies with ultrasound imaging.

Fat tissue equivalent phantoms for microwave applications by reinforcing gelatin with nanocellulose

Tissue mimicking phantom materials with thermal and dielectric equivalence are vital for the development of microwave diagnostics and treatment. The current phantoms representing fat tissue are challenged by mechanical integrity at relevant temperatures coupled with complex production protocols. We have employed two types of nanocellulose (cellulose nanocrystals and oxidized cellulose nanocrystals) as reinforcement in gelatin stabilized emulsions for mimicking fat tissue. The nanocellulose-gelatin stabilized emulsions were evaluated for their dielectric properties, the moduli-temperature dependence using small deformation rheology, stress-strain behavior using large deformation, and their compliance to quality assurance guidelines for superficial hyperthermia. All emulsions had low permittivity and conductivity within the lower microwave frequency band, accompanied by fat equivalent thermal properties. Small deformation rheology showed reduced temperature dependence of the moduli upon addition of nanocellulose, independent of type. The cellulose nanocrystals gelatin reinforced emulsion complied with the quality assurance guidelines. Hence, we demonstrate that the addition of cellulose nanocrystals to gelatin stabilized emulsions has the potential to be used as fat phantoms for the development of microwave diagnostics and treatment.

3-D H-Scan Ultrasound Imaging and Use of a Convolutional Neural Network for Scatterer Size Estimation

H-Scan ultrasound (US) is a new imaging technology that estimates the relative size of acoustic scattering objects and structures. The purpose of this study was to introduce a three-dimensional (3-D) H-scan US imaging approach for scatterer size estimation in volume space. Using a programmable research scanner (Vantage 256, Verasonics Inc, Kirkland, WA, USA) equipped with a custom volumetric imaging transducer (4 DL7, Vermon, Tours, France), raw radiofrequency (RF) data was collected for offline processing to generate H-scan US volumes. A deep convolutional neural network (CNN) was modified and used to achieve voxel mapping from the input H-scan US image to underlying scatterer size. Preliminary studies were conducted using homogeneous gelatin-based tissue-mimicking phantom materials embedded with acoustic scatterers of varying size (15 to 250 μm) and concentrations (0.1 to 1%). Two additional phantoms were embedded with 63 or 125 µm-sized microspheres and used to test CNN estimation accuracy. In vitro results indicate that 3-D H-scan US imaging can visualize the spatial distribution of acoustic scatterers of varying size at different concentrations (R2 > 0.85, p < 0.03). The result of scatterer size estimation reveals that a CNN can achieve an average mapping accuracy of 93.3%. Overall, our preliminary in vitro findings reveal that 3-D H-scan US imaging allows the visualization of tissue scatterer patterns and incorporation of a CNN can be used to help estimate size of the acoustic scattering objects.

Characterization of Nylon-12 as a water-equivalent solid phantom material for dosimetric measurements in therapeutic photon and electron beams

The tissue- or water-equivalence of dosimetry phantoms used as substitutes for water is essential for absorbed dose measurements in radiotherapy. At our institution, a heterogeneous pelvic phantom that consists of stacked Nylon-12 layers has recently been manufactured for Gafchromic film dosimetry. However, data on the use of Nylon as tissue-mimicking media for dosimetric applications are scarce. This study characterizes the water-equivalence of Nylon-12 for dosimetric measurements in therapeutic photon and electron beams. Employing an Elekta Synergy and SL25 linear accelerator (Linac), photon beam transmission measurements for 6 MV and 15 MV, acquired in narrow beam geometry with a 0.6 cm3 Farmer-type ion chamber showed that the mass attenuation coefficient μm of Nylon-12 agrees with the values of water, water-equivalent RW3 and Perspex phantom materials within 3%. For 6 MV, the μm values were 0.0477 ± 0.002 cm2/g, 0.0490 ± 0.003 cm2/g, 0.0482 ± 0.001 cm2/g and 0.0479 ± 0.002cm2/g for Nylon-12, water, RW3, and Perspex, respectively. Differences within 2% were attained between depth dose data measured in Nylon-12 slabs with Gafchromic EBT3 films and in water with a Roos ion chamber for 10 × 10 cm2 6, 12 and 20 MeV electron beams produced by the Elekta Synergy and SL25 Linacs. Also, a good agreement within 2% was obtained between percent depth doses computed by DOSXYZnrc Monte Carlo simulations in water, Nylon-12 and RW3 materials for photon spectra between 250 kV and 15 MV. The discrepancies between the ratios of average, restricted stopping powers of Nylon to air and water to air for photon spectra ranging from 2 to 45 MV are typically within 1% signifying that Nylon and water have equivalent stopping power characteristics. This study highlights that Nylon-12 can be used as a tissue-mimicking phantom material for dosimetric measurements in clinical megavoltage photon and electron beams as it exhibits good water-equivalence.

Quantitative magnetic resonance elastography for polymer-gel dosimetry phantoms

Commonly dose-responses of conventional dosimetric methods are affected by a saturation dose and are known to be limited when the delivered dose is relatively high. In contrast, elastic properties of polymer-gel dosimeter phantoms play major roles in a new dosimetry technique using magnetic resonance elastography (MRE). A single volume of polymer-gel dosimeter solution containing methacrylic and ascorbic acid in gelatin initiated by copper was prepared. The material was subsequently stored in cylindrical containers for future use as a biological tissue-mimicking phantom material. The phantom material was irradiated with gamma rays, where absorbed doses of 10–50 Gy were delivered. To study the dynamic elastic behaviour, periodic mechanical external forces of 100–400 Hz were applied to generate shear waves in the samples. The radiation-induced changes in the shear modulus of the samples were estimated from wave-displacement images and converted to elastograms. The smallest and largest shear modulus values were approximately 2.10 ± 0.64 and 35.26 ± 2.85 kPa, respectively. The dynamic elastic response of the polymer-gel dosimeters showed an increased dependency with frequency. A linear relationship (R2 = 0.996) was observed between the integrated area and the absorbed dose of the samples. The elastograms clearly showed that the largest shear modulus values were in the irradiated region of the polymer-gel dosimeter phantoms. Quantitative values of the shear modulus of polymer-gel dosimeters were estimated using MRE.

Real-time H-scan ultrasound imaging using a Verasonics research scanner

H-scan ultrasound (US) is a new imaging technique that relies on matching a model that describes US image formation to the mathematics of a class of Gaussian-weighted Hermite polynomials (GH). In short, H-scan US (where the ‘H’ denotes Hermite or hue) is a tissue classification technique that images the relative size of acoustic scatterers. Herein, we detail development of a real-time H-scan US imaging technology that was implemented on a programmable US research scanner (Vantage 256, Verasonics Inc, Kirkland, WA). This custom US imaging system has a dual display for real-time visualization of both the H-scan and B-scan US images. This MATLAB-based (Mathworks Inc, Natick, MA) system includes a graphical user interface (GUI) for controlling the entire US scan sequence including the raw radio frequency (RF) data acquisition parameters, image processing, variable control of a parallel set of convolution filters used to derive the H-scan US signal, and data (cine loop) save. The system-level structure used for software-based image reconstruction and display is detailed. Imaging studies were conducted using a series of homogeneous and heterogeneous tissue-mimicking phantom materials embedded with monodisperse spherical US scatterers of size 15–40 µm in diameter. Relative to H-scan US image measurements from a phantom with 15 µm-sized scatterers, data from phantoms with the 30 and 40 µm-sized scatterers exhibited mean intensity increases of 5.2% and 11.6%, respectively. Overall, real-time H-scan US imaging is a promising approach for visualizing the relative size and distribution of acoustic scattering objects.

The Effect of Paramagnetic Agent on Relaxation and Mechanical Properties of Agar Hydrogel for Phantom in Magnetic Resonance Imaging

Agar hydrogel is largely used in magnetic resonance imaging study as tissue mimicking phantom material for its cost-effectiveness and easy preparation. Spin-spin relaxation time, T2 is one important parameter in Magnetic Resonance Imaging study. However, T2 of agar sample is higher than those of human tissues. The addition of paramagnetic agent such as copper sulphate or CuSO4 had been observed to match T2-value of human tissues. In this study, the effect of CuSO4 on relaxation and mechanical properties of agar is observed.

Estimates for the acoustical stimulation and heating of multiphase biotissue.

Low-intensity, unfocused, ultrasound-induced diathermy can produce undesired temperature increases at the interface of adjacent tissues within the body; particularly, at the interface of soft tissue and bone. This study provides a computational framework for predicting an upper bound on the temperature profile within a multiphase system composed of gel pad (water), tissue and bone from an input of acoustic energy, at frequencies and power levels consistent with applications of therapeutic hyperthermia. The model consists of solving a (one-dimensional) spatially discretized bioheat transfer equation via finite-difference method and updating the solution in time with a forward-Euler scheme. Simulations are then compared to experimental data to determine the energy-to-heat conversion factors within each constituent material using thermocouple-embedded, tissue-mimicking phantom material, with and without bone. Viscous heating artifacts from the presence of the thermocouples in the experimental phantom tissue are accounted for via additional experimental methods similar to those described by Morris et al. (Phys Med Biol 53:4759, 2008). Finally, an example application of the model is presented via prediction of the maximum temperature at the tissue-bone interface, as well as the peak temperatures in the composite structure at the end of a prescribed 2-min sonication, of blood-perfused, human soft-tissue at 1, 2 and 3MHz frequencies and a spatial peak temporally averaged intensity of [Formula: see text]. The results of this simulation are then related to comparable experimental studies in the literature.

Effects of needle inner surface topography on friction and biopsy length

The effects of inner surface topography on friction force and the coefficient of friction between an inner surface of needle and tissue phantom during needle insertion and on biopsy length are examined using polished, and unpolished needles. In this paper, the inner surfaces of the needles are altered by magnetic abrasive finishing (MAF), and the needle inner surfaces were smoothed from 0.43 to 0.02µm Sa (referred to as the smoothly polished needle) or 0.26µm Sa (referred to as the roughly polished needle). With polyvinyl chloride (PVC) as a tissue-mimicking phantom material, the smoothly polished needle results in the smallest inner friction force (0.0024N/mm), the smallest coefficient of friction (0.35), and the longest biopsy length (34.3mm). The roughly polished needle produces the largest inner friction force (0.0041N/mm), the largest coefficient of friction (0.56), and the shortest biopsy length (30.5mm). Although the inner surface roughness of the roughly polished needle is lower than that of the unpolished needle, the inner friction force and coefficient of friction are larger than those of the unpolished needle. This may be caused by the ridges and grooves in the circumferential direction of the roughly polished needle made with MAF. Based on the surface topography data, the ratchet mechanism is utilized to calculate the coefficient of friction. The results suggest a higher coefficient of friction in the roughly polished needle. The biopsy tests also show the shortest biopsy sample is extracted using the roughly polished needles, which exhibit the greatest inner friction force.

Development and modelling of the dielectric properties of tissue-mimicking phantom materials for ultra-wideband microwave breast cancer detection

In this paper, development and characterization of oil-in-gelatin dispersions are recommended that approximate the dispersive dielectric properties of different human soft tissues over the microwave frequency range from 0.5GHz to 20GHz. Different tissues are mimicked by selection of an appropriate concentration of oil. Thus, these materials can be used to construct heterogeneous phantoms including anthropomorphic types for ultra-wideband microwave breast cancer detection and imaging systems. The dielectric constant of the human tissues decreases from low to high frequencies. The experimental data are analyzed and relevant dielectric parameters are determined by curve fitting. It is concluded that bioelectric modelling provides a useful tool in the development of different human tissue mimicking mediums and complex structured phantom to be used for the breast cancer detection.

Modeling the effects of biological tissue on RF propagation from a wrist-worn device.

Many wireless devices in common use today are worn either on or in close proximity to the body. Among them are a growing number of wrist-mounted devices designed for applications such as activity or vital-signs monitoring, typically using Bluetooth technology to communicate with external devices. Here, we use a tissue-mimicking phantom material in conjunction with anechoic chamber and network analyzer testing to investigate how antenna propagation patterns in one such device are influenced by the electrical properties of the human wrist. A microstrip antenna module is mounted onto phantom material of various geometries, and the resulting voltage standing wave ratio (VSWR), input impedance, and azimuth radiation pattern are recorded in both free space and real-world environments. The results of this study demonstrate how the high permittivity values of human tissue (ε(r) ≈ 16) affect the design parameters of microstrip antennas. A simulation environment using Sonnet EM software was used to further analyze the high dielectric effects of biological tissue on RF propagation.

Multi-modality gellan gum-based tissue-mimicking phantom with targeted mechanical, electrical, and thermal properties

This study develops a new class of gellan gum-based tissue-mimicking phantom material and a model to predict and control the elastic modulus, thermal conductivity, and electrical conductivity by adjusting the mass fractions of gellan gum, propylene glycol, and sodium chloride, respectively. One of the advantages of gellan gum is its gelling efficiency allowing highly regulable mechanical properties (elastic modulus, toughness, etc). An experiment was performed on 16 gellan gum-based tissue-mimicking phantoms and a regression model was fit to quantitatively predict three material properties (elastic modulus, thermal conductivity, and electrical conductivity) based on the phantom material's composition. Based on these material properties and the regression model developed, tissue-mimicking phantoms of porcine spinal cord and liver were formulated. These gellan gum tissue-mimicking phantoms have the mechanical, thermal, and electrical properties approximately equivalent to those of the spinal cord and the liver.

Impedance of tissue-mimicking phantom material under compression

Abstract The bioimpedance of tissues under compression is a field in need of study. While biological tissues can become compressed in a myriad of ways, very few experiments have been conducted to describe the relationship between the passive electrical properties of a material (impedance/admittance) and its underlying mechanical properties (stress and strain) during deformation. Of the investigations that have been conducted, the exodus of fluid from samples under compression has been thought to be the cause of changes in impedance, though until now was not measured directly. Using a soft tissue-mimicking phantom material (tofu) whose passive electrical properties are a function of the conducting fluid held within its porous structure, we have shown that the mechanical behavior of a sample under compression can be measured through bioimpedance techniques.

Wideband MR elastography for viscoelasticity model identification

The growing clinical use of MR elastography requires the development of new quantitative standards for measuring tissue stiffness. Here, we examine a soft tissue mimicking phantom material (Ecoflex) over a wide frequency range (200 Hz to 7.75 kHz). The recorded data are fit to a cohort of viscoelastic models of varying complexity (integer and fractional order). This was accomplished using multiple sample sizes by employing geometric focusing of the shear wave front to compensate for the changes in wavelength and attenuation over this broad range of frequencies. The simple axisymmetric geometry and shear wave front of this experiment allows us to calculate the frequency-dependent complex-valued shear modulus of the material. The data were fit to several common models of linear viscoelasticity, including those with fractional derivative operators, and we identified the best possible matches over both a limited frequency band (often used in clinical studies) and over the entire frequency span considered. In addition to demonstrating the superior capability of the fractional order viscoelastic models, this study highlights the advantages of measuring the complex-valued shear modulus over as wide a range of frequencies as possible.

A heterogeneous human tissue mimicking phantom for RF heating and MRI thermal monitoring verification

This paper describes a heterogeneous phantom that mimics a human thigh with a deep-seated tumor, for the purpose of studying the performance of radiofrequency (RF) heating equipment and non-invasive temperature monitoring with magnetic resonance imaging (MRI). The heterogeneous cylindrical phantom was constructed with an outer fat layer surrounding an inner core of phantom material mimicking muscle, tumor and marrow-filled bone. The component materials were formulated to have dielectric and thermal properties similar to human tissues. The dielectric properties of the tissue mimicking phantom materials were measured with a microwave vector network analyzer and impedance probe over the frequency range of 80–500 MHz and at temperatures of 24, 37 and 45 °C. The specific heat values of the component materials were measured using a differential scanning calorimeter over the temperature range of 15–55 °C. The thermal conductivity value was obtained from fitting the curves obtained from one-dimensional heat transfer measurement. The phantom was used to verify the operation of a cylindrical four-antenna annular phased array extremity applicator (140 MHz) by examining the proton resonance frequency shift (PRFS) thermal imaging patterns for various magnitude/phase settings (including settings to focus heating in tumors). For muscle and tumor materials, MRI was also used to measure T1/T2* values (1.5 T) and to obtain the slope of the PRFS phase change versus temperature change curve. The dielectric and thermal properties of the phantom materials were in close agreement to well-accepted published results for human tissues. The phantom was able to successfully demonstrate satisfactory operation of the tested heating equipment. The MRI-measured thermal distributions matched the expected patterns for various magnitude/phase settings of the applicator, allowing the phantom to be used as a quality assurance tool. Importantly, the material formulations for the various tissue types may be used to construct customized phantoms that are tailored for different anatomical sites.

Rayleigh–Lamb wave propagation on a fractional order viscoelastic plate

A previous study of the authors published in this journal focused on mechanical wave motion in a viscoelastic material representative of biological tissue [Meral et al., J. Acoust. Soc. Am. 126, 3278-3285 (2009)]. Compression, shear and surface wave motion in and on a viscoelastic halfspace excited by surface and sub-surface sources were considered. It was shown that a fractional order Voigt model, where the rate-dependent damping component that is dependent on the first derivative of time is replaced with a component that is dependent on a fractional derivative of time, resulted in closer agreement with experiment as compared with conventional (integer order) models, such as those of Voigt and Zener. In the present study, this analysis is extended to another configuration and wave type: out-of-plane response of a viscoelastic plate to harmonic anti-symmetric Lamb wave excitation. Theoretical solutions are compared with experimental measurements for a polymeric tissue mimicking phantom material. As in the previous configurations the fractional order modeling assumption improves the match between theory and experiment over a wider frequency range. Experimental complexities in the present study and the reliability of the different approaches for quantifying the shear viscoelastic properties of the material are discussed.

Evaluation of three-dimensional temperature distributions produced by a low-frequency transcranial focused ultrasound system within ex vivo human skulls

Transcranial MR-guided focused ultrasound (TcMRgFUS) provides a potential noninvasive alternative to surgical resection and for other treatments for brain disorders. Use of low-frequency ultrasound provides several advantages for TcMRgFUS, but is potentially limited by reflection and standing wave effects that may cause secondary hotspots within the skull cavity. The purpose of this work was to use volumetric magnetic resonance temperature imaging (MRTI) and ex vivo human skulls filled with tissue-mimicking phantom material to search for heating distant from the focal point that may occur during sonication with a TcMRgFUS system as a result of reflections or standing wave effects. Heating during 120-s sonications was monitored within the entire skull volume for 12 different locations in two different skulls. The setup used a hemispheric array operating at 220 kHz. Multiple sonications were delivered at each location while varying the MRTI slice positions to provide full coverage of the skull cavity. An automated routine was used evaluate the MRTI to detect voxel regions that appeared to be heated by ultrasound. No secondary hotspots with a temperature rise of 15% or more of the focal heating were found. The MRTI noise level prevented the identification of possible hotspots with a lower temperature rise. These results suggest that significant secondary heating by this TcMRgFUS system at points distant from the focal point are not common.

Non-invasive ultrasound-based temperature imaging for monitoring radiofrequency heating—phantom results

Minimally invasive therapies (such as radiofrequency ablation) are becoming more commonly used in the United States for the treatment of hepatocellular carcinomas and liver metastases. Unfortunately, these procedures suffer from high recurrence rates of hepatocellular carcinoma (∼34–55%) or metastases following ablation therapy. The ability to perform real-time temperature imaging while a patient is undergoing radiofrequency ablation could provide a significant reduction in these recurrence rates. In this paper, we demonstrate the feasibility of ultrasound-based temperature imaging on a tissue-mimicking phantom undergoing radiofrequency heating. Ultrasound echo signals undergo time shifts with increasing temperature, which are tracked using 2D correlation-based speckle tracking methods. Time shifts or displacements in the echo signal are accumulated, and the gradient of these time shifts are related to changes in the temperature of the tissue-mimicking phantom material using a calibration curve generated from experimental data. A tissue-mimicking phantom was developed that can undergo repeated radiofrequency heating procedures. Both sound speed and thermal expansion changes of the tissue-mimicking material were measured experimentally and utilized to generate the calibration curve relating temperature to the displacement gradient. Temperature maps were obtained, and specific regions-of-interest on the temperature maps were compared to invasive temperatures obtained using fiber-optic temperature probes at the same location. Temperature elevation during a radiofrequency ablation procedure on the phantom was successfully tracked to within ±0.5 °C.