Institute of Fundamental Technological Research

Recently, magneto-ultrasound heating of tissue in the presence of magnetic nanoparticles (NPs) has been studied due to its high potential for use in oncological hyperthermia. It has been published that a synergistic effect, generation of additional heat caused by magneto-ultrasonic coupling, was observed in a tissue-mimicking material (TMM) enriched with magnetic NPs. The specific absorption rate (SAR) was determined from the temperature rise measurements in a focus of the ultrasound beam. It is important to use precise measurement methods when considering medical applications, for which there are limitations to the power of each field, resulting from the prevention of biological phenomena dangerous to the patient. This study demonstrates that in magneto-ultrasonic heating SAR can be measured much more accurately if the ultrasonic field is almost uniform. Measurements were performed on TMM containing Fe3O4 NPs with a diameter of approximately 8 nm and superparamagnetic properties. Both, the measurement and simulation results showed that the errors resulting from the inaccuracy of placing the temperature probe are smaller than in the case of the focused ultrasound. At the same time, the temperature increase caused by the ultrasonic field is almost linear and the influence of heat convection on the SAR determination is negligible. The measurements showed that magneto-ultrasonic hyperthermia can provide the desired thermal effect at lower ultrasound powers and magnetic fields compared to ultrasonic or magnetic hyperthermia used alone. No synergy effect was recorded.

Magnetic nanoparticle-mediated hyperthermia,Dual-mode ultrasonic-magnetic hyperthermia,Specific absorption rate,Hyperthermia efficiency

Temperature monitoring in ultrasound (US) imaging is important for various medical treatments, such as high-intensity focused US (HIFU) therapy or hyperthermia. In this work, we present a deep learning based approach to temperature monitoring based on radio-frequency (RF) US data. We used Siamese neural networks in an unsupervised way to spatially compare RF data collected at different time points of the heating process. The Siamese model consisted of two identical networks initially trained on a large set of simulated RF data to assess tissue backscattering properties. To illustrate our approach, we experimented with a tissue-mimicking phantom and an ex-vivo tissue sample, which were both heated with a HIFU transducer. During the experiments, we collected RF data with a regular US scanner. To determine spatiotemporal variations in temperature distribution within the samples, we extracted small 2D patches of RF data and compared them with the Siamese network. Our method achieved good performance in determining the spatiotemporal distribution of temperature during heating. Compared with the temperature monitoring based on the change in radio-frequency signal backscattered energy parameter, our method provided more smooth spatial parametric maps and did not generate ripple artifacts. The proposed approach, when fully developed, might be used for US based temperature.

temperature monitoring, high intensity ultrasound, deep learning, transfer learning, ultrasound imaging

Magnetic nanoparticles (MNP)s of Fe3O4 were synthesized in the co-precipitation reaction of iron chlorides dissolved in water and ammonia water. To produce polyethylene glycol (PEG) coatings of the NMPs, we added PEG to the ammonia water during the fabrication process. Magnetic fluids, ferrofluids, for research were prepared as oleic acid suspension of bare and PEG-coated nanoparticles at four concentrations. The results of the conducted calorimetric experiments confirmed that the efficiency of heating ferrofluids strongly depends on the concentration of nanoparticles in fluids. The results also indicate that the ferrofluids containing PEG-coated NPs heat up more than ferrofluids with bare nanoparticles. They are characterized by a higher specific absorption rate (SAR) value calculated from the initial slope of temperature versus time curve during heating. 10.1016/j.jmmm.2021.168918, 10.1016/j.jmmm.2022.169422

nanoparticle fluid hyperthermia, magnetite nanoparticles, PEG-coated nanoparticles, hyperthermia

Magnetic nanoparticles-mediated hyperthermia was widely studied in the last decades as applicable in cancer therapy. The majority of magnetic hyperthermia research was devoted to improvement of heating efficiency by application of various nanomaterials. The influence of biocompatibility, magnetic properties, sizes, composition, and concentration of magnetic nanoparticles (MNPs) on hyperthermia efficiency was extensively studied. Also, the limits preserving biological safety and the chemical stability of MNPs delivered to the tissue were established. However, much less research concerned the impact of the physical interactions between the closest MNPs on the hyperthermia efficiency. Our goal was to demonstrate the relationships between the internal structure of soft tissue containing MNPs, and the thermal effects of an alternating magnetic field. Because agarose-based gel exhibits a tissue-like internal structure, we performed hyperthermia experiments in two types of such gel containing bare and polyethylene glycol-coated Fe3O4 nanoparticles. We described the structural difference and we estimated the ferrogels specific absorption rate coefficients (SAR) from calorimetric experiments. Magnetic measurements showed 11% lower magnetic saturation of PEG-coated MNPs than of the bare MNPs. While the SAR of ferrogel with PEG-coated MNPs was 15% greater than bare MNPs. The structural characteristics calculated from TEM and SEM images were significantly different. Particularly, we observed the nanoparticle agglomeration in the gel with bare MNPs. The bare MNPs uniformly packed and located inside agarose double helices were observed for the first time. The distribution of MNPs and their spatial configuration in gel influenced strongly the strength of bonds blocking the movement of MNPs and determined the ferrogels heating efficiency. As the tissues to which we delivered MNPs were composed of agarose gel-like structures, our results may be useful in further research on hyperthermia in vivo. 10.1016/j.jmmm.2021.169000, 10.1016/j.jmmm.2022.169423

nanoparticle-mediated magnetic hyperthermia, ferrogel, nanoparticles distribution, double helices structure

Kidney Cooling Jacket (KCJ) preserves the kidney graft, wrapped in the jacket, against the too fast time of temperature rise during the operation of connecting a cooled transplant to the patient’s bloodstream. The efficiency of KCJ depends on the stationarity of the fluid flow and its spatial uniformity. In this paper, the fluid velocity field inside the three different KCJ prototypes has been measured using the 20 MHz ultrasonic Doppler flowmeter. The simplified 2D geometrical model of the prototypes has been presented using COMSOL-Multiphysics to simulate the fluid flow assuming the laminar flow model. By comparing the numerical results with experimental data, the simplified 2D model is shown to be accurate enough to predict the flow distribution of the internal fluid velocity field within the KCJ. The discrepancy between the average velocity measured using the 20 MHz Doppler and numerical results was mainly related to the sensitivity of the velocity measurements to a change of the direction of the local fluid flow stream. Flux direction and average velocity were additionally confirmed by using ommercial colour Doppler imaging scanner. The current approach showed nearly 90% agreement of the experimental results and numerical simulations. It was important for justifying the use of numerical modelling in designing the baffles distribution (internal walls in the flow space) for obtaining the
most spatially uniform field of flow velocity.

multi-canal system; fluid flow prediction; cooling jacket; flow Doppler measurement

Magnetic nanoparticle’s different applications in nanomedicine, due to their unique physical properties and biocompatibility, were intensively investigated. Recently, Fe3O4 nanoparticles, are confirmed to be the best sonosensitizers to enhance the performance of HIFU (high intensity focused ultrasound). They are also used as thermo-sensitizers in magnetic hyperthermia. A new idea of dual, magneto-ultrasound, coupled hyperthermia allows the ultrasound intensity to be reduced from the high to a moderate level. Our goal is to evaluate the enhancement of thermal effects of focused ultrasound of moderate intensity due to the presence of nanoparticles. We combine experimental results with numerical analysis. Experiments are performed on tissue-mimicking materials made of the 5% agar gel and gel samples containing Fe3O4 nanoparticles with φ = 100 nm with two fractions of 0.76 and 1.53% w/w. Thermocouples registered curves of temperature rising during heating by focused ultrasound transducer with acoustic powers of the range from 1 to 4 W. The theoretical model of ultrasound-thermal coupling is solved in COMSOL Multiphysics. We compared the changes between the specific absorption rates (SAR) coefficients determined from the experimental and numerical temperature rise curves depending on the nanoparticle fractions and applied acoustic powers.We confirmed that the significant role of nanoparticles in enhancing the thermal effect is qualitatively similarly estimated, based on experimental and numerical results. So that we demonstrated the usefulness of the FEM linear acoustic model in the planning of efficiency of nanoparticle-mediated moderate hyperthermia.

ultrasonic hyperthermia, agar-based tissue mimicking phantom, magnetic nanoparticles, temperature, specific absorption rate (SAR)

Breast cancer is one of the most common women's cancers, so an available diagnostic modality, particularly non-invasive, is important. Infrared thermography (IRT) is a supporting diagnostic modality. Until now, many finite element methods (FEM) numerical models have been constructed to evaluate IRT's diagnostic value and to relate breast skin temperature characteristics with breast structural disorder presence, particularly to distinguish between cancerous types and normal structures. However, most of the models were not based on any clinical data, except for several papers based on clinical magnetic resonance imaging (MRI) data, wherein a three-dimensional (3D) breast model was studied. In our paper, we propose a very simplified numerical two-dimensional FEM model constructed based on clinical ultrasound data of breasts, which is much cheaper and available in realtime as opposed to MRI data. We show that our numerical simulations enabled us to distinguish between types of healthy breasts in agreement with the clinical classification and with thermographic results. The numerical breast models predicted the possibility of differentiation of cancerous breasts from healthy breasts by significantly different skin temperature variation ranges. The thermal variations of cancerous breasts were in the range of 0.5 8C–3.0 8C depending on the distance of the tumor from the skin surface, its size, and the cancer type. The proposed model, due to its simplicity and the fact that it was constructed based on clinical ultrasonographic data, can compete with the more sophisticated 3D models based on MRI.

non-invasive cancer detection, Pennes' bioheat transfer equation, finite element method, breast thermography, ultrasonography

Purpose: Nowadays, the improvement of ultrasonic hyperthermia therapy is often achieved by adding hard particles to the sonicated medium in order to increase the heating efficiency. The explanation of the phenomenon of ultrasonic heating still requires testing on tissue mimicking materials (TMMs), enriched with particles of different sizes and physical properties. Our goal was to determine, by comparing their quantitative acoustic properties, which TMMs, with magnetic micro- or nanoparticles, convert more ultrasonic energy into heat or which of the particles embedded in the agar gel act as more effective thermal sonosensitizers. Methods: We manufactured a pure agar gel and an agar gel with the addition of magnetic micro- or nanoparticles in two proportions of 8 and 16 mg/ml. Ultrasound quantitative techniques, the broadband reflection substitution technique and backscattered spectrum analysis were used to characterize the samples by speed of sound (SOS), frequency-dependent attenuation, and backscattering coefficients. The integrated backscattering coefficients were also calculated. The quantitative parameters, scattering, and attenuation coefficients of ultrasound in phantoms with micro- and nanoparticles were estimated. Based on the attenuation and scattering of ultrasound in the samples, the ultrasonic energy absorption, which determines the heating efficiency, was evaluated. Additionally, the temperature increase during sonication of the phantoms by an ultrasonic beam was directly measured using thermocouples. Results: The density of the materials with nanoparticles was higher than for the materials with microparticles with the same fractions of particles. The SOS for all materials ranged from 1489 to 1499 m/s. The attenuation in the whole frequency range (3–8 MHz) was higher for the materials with nanoparticles than for the materials with microparticles. For the materials with the lower content (8 mg/ml) of particles, the attenuation coefficient was 0.2 dB/(MHz cm). For the 16 mg/ml concentration of nanoparticles and microparticles, the attenuation coefficients were 0.66 and 0.45 dB/(MHz cm), resectively. The value of backscattering coefficient in the whole frequency range was greater for the materials with microparticles than for the materials with nanoparticles. The values of the integrated backscattering coefficient were 0.05 and 0.08 1/m for the materials with nanoparticles and 0.46 and 0.82 1/m for the materials with microparticles and concentrations of 8 and 16 mg/ml, respectively. The rates of temperature increase in the first 3 s due to ultrasonic heating were higher for the materials with nanoparticles than for the materials with microparticles. Conclusions: Based on acoustical measurements, we confirmed that all materials can be used as tissue phantoms in the study of ultrasonic hyperthermia, as their properties were in the range of soft tissue properties. We found that the nanoparticle-doped materials had greater attenuation and smaller scattering of ultrasound than the materials with microparticles, so absorption in these materials is greater. Thus, the TMMs with nanoparticles convert more acoustic energy into heat and we conclude that magnetic nanoparticles are more effective thermal sonosensitizers than microparticles. This conclusion is confirmed by direct measurement of the temperature increase in the samples subjected to sonification.

backscattering coefficient, frequency-dependent attenuation, hyperthermia TMM, magnetic particles, ultrasound absorption

Temperature monitoring is essential for various medical treatments. In this work, we investigate the impact of temperature on backscattered ultrasound echo statistics during a high intensity focused ultrasound treatment. A tissue mimicking phantom was heated with a spherical ultrasonic transducer up to 56 _C in order to imitate tissue necrosis. During the heating, an imaging scanner was used to acquire backscattered echoes from the heated region. These data was then modeled with the homodyned K distribution. We found that the best temperature indicator can be obtained by combining two parameters of the model, namely the backscattered echo mean intensity and the effective number of scatterers per resolution cell. Next, ultrasonic thermometer was designed and used to create a map of the temperature induced within the tissue phantom during the treatment

Temperature monitoring, homodyned K distribution, focused ultrasound

Texture of ultrasound images contain information about the properties of examined tissues. The analysis of statistical properties of backscattered ultrasonic echoes has been recently successfully applied to differentiate healthy breast tissue from the benign and malignant lesions. We propose a novel procedure of tissue characterization based on acquiring backscattered echoes from the heated breast. We have proved that the temperature increase inside the breast modifies the intensity, spectrum of the backscattered signals and the probability density function of envelope samples. We discuss the differences in probability density functions in two types of tissue regions, e.g. cysts and the surrounding glandular tissue regions. Independently, Pennes bioheat equation in heterogeneous breast tissue was used to describe the heating process. We applied the finite element method to solve this equation. Results have been compared with the ultrasonic predictions of the temperature distribution. The results confirm the possibility of distinguishing the differences in thermal and acoustical properties of breast cyst and surrounding glandular tissues.

medical ultrasound, temperature changes in vivo, breast tissue, ultrasonic temperature measurement

Polyvinyl-alcohol cryogel is commonly used for soft tissue phantom manufacture. The gel formation from an aqueous solution of polyvinyl-alcohol takes place during the freezing and thawing cycle. The aim of this work was to assess the degree of gel solidification, hence the material stiffness, by means of quantitative ultrasound. We manufactured three phantoms which differed in the number of freezing/thawing cycles. First, tissue phantoms were examined with an elastography technique. Next, we measured the speed of sound and the attenuation coefficient. What is more, the inter structure variations in phantoms were assessed with the Nakagami imaging which quantifies the scattering properties of the backscattered ultrasound echo. Obtained results confirmed the connection between the number of freezing/thawing cycles and the solidification process. We defined the boundary layer as a region which has a different structure than the sample interior. Next, for each phantom this layer was extracted based on a Nakagami parameter map. We calculated that the thickness of the boundary layer was lower in samples which were subjected to a larger number of freezing/thawing cycles.

soft tissue phantoms, elastography, ultrasound attenuation, speed of sound, Nakagami maps, stiffness

A novel estimation of temperature changes inside soft tissues has been proposed in sub-ablation range, i.e. 20°C-48°C. This estimation has been obtained by studying statistical properties of backscattered ultrasonic signals. Two different procedures of heating/cooling have been performed in which the RF echoes have been registered from soft tissue phantom in the first procedure, and from soft tissue in vitro in the second one. Calculated envelopes of signals registered in time points during heating/cooling experiments have been treated as a statistical sample drawn from a random variable with three different distributions, namely the Rayleigh distribution, the Nakagami distribution, and the K-distribution. The histograms obtained in subsequent time moments have been fitted to the three distributions. Dependencies of their shape and scale parameters on temperature have been calculated. It is concluded that the shape parameter of the K-distribution can be chosen as the best marker of temperature changes in both experiments. The choice of the marker has been made by analysis of temperature dependencies of all calculated parameters and by comparing the quality of fitting all histograms to the considered distributions. Besides, the chosen marker as a function of temperature exhibits the closest shape to temperature/time function experimentally measured.

therapeutic applications, ultrasonics, medical imaging

There are two main topics of this research: (i) one topic considers overall properties of a nonlinear cellular composite, treated as a model of the liver tissue, and (ii) the other topic concerns the propagation of heat in the nonlinear medium described by the homogenised coefficient of thermal conductivity.

For (i) we give a method and find the effective thermal conductivity for the model of the liver tissue, and for the point (ii) we present numerical and analytical treatment of the problem, and indicate the principal difference of heat propagation in linear and nonlinear media. In linear media, as it is well known, the range of the heat field is infinite for all times t > 0, and in nonlinear media it is finite.

Pennes’ equation, which should characterize the heat propagation in the living tissue, is in general a quasi-nonlinear partial differential equation, and consists of three terms, one of which describes Fourier’s heat diffusion with conductivity being a function of temperature T. This term is just a point of our analysis.

We show that a nonlinear character of the medium (heat conductivity dependent on the temperature) changes in qualitative manner the nature of heat transfer. It is proved that for the heat source concentrated initially (t = 0) at the space point, the range of heated region (for t > 0) is finite. The proof is analytical, and illustrated by a numerical experiment.

heat transport, asymptotic homogenisation, effective heat conductivity

The study shows the direct relationship between the temperature field and the parallel changes that are taking place in backscattered ultrasonic signals from the breast tissue in vivo when heated to the temperature of approximately 42 o C. The non-uniform temperature field inside the heating tissue was determined by the numerical model using FEM. It is shown that the spatial distribution of intensities of the backscattered signals coincides with the temperature distribution field predicted by the numerical model in some areas. The result indicates the possibility of the indirect measurement of the temperature rise in the breast tissue in vivo by measuring the intensity variations of the ultrasound echo.

temperature field, backscattered ultrasonic signals, breast tissue in vivo, FEM model

A tissue thermal conductivity (Ks) is an important parameter which knowledge is essential whenever thermal fields induced in selected organs are predicted. The main objective of this study was to develop an alternative ultrasonic method for determining Ks of tissues in vitro suitable for living tissues. First, the method involves measuring of temperature-time T(t) rises induced in a tested tissue sample by a pulsed focused ultrasound with measured acoustic properties using thermocouples located on the acoustic beam axis. Measurements were performed for 20-cycle tone bursts with a 2 MHz frequency, 0.2 duty-cycle and 3 different initial pressures corresponding to average acoustic powers equal to 0.7 W, 1.4 W and 2.1 W generated from a circular focused transducer with a diameter of 15 mm and f-number of 1.7 in a two-layer system of media: water/beef liver. Measurement results allowed to determine position of maximum heating located inside the beef liver. It was found that this position is at the same axial distance from the source as the maximum peak-peak pressure calculated for each nonlinear beam produced in the two-layer system of media. Then, the method involves modeling of T(t) at the point of maximum heating and fitting it to the experimental data by adjusting Ks. The averaged value of Ks determined by the proposed method was found to be 0.5±0.02 W/(m·°C) being in good agreement with values determined by other methods. The proposed method is suitable for determining Ks of some animal tissues in vivo (for example a rat liver).

Acoustics, Sound pressure, Beef, Thermal conductivity, Thermocouples, Nonlinear systems, Sound waves, Bioacoustics

The aim of the paper is to find links between the dynamics of changes of statistical parameters and changes in spectral properties of the signal envelope of backscattered RF signals during the thermal process. We have shown previously that by using wavelet approximations these tendencies are better recognized in the case of the heating of a phantom sample than in the parallel analysis performed for a full signal envelope. Here we are currently expanding this statement to the case of heating a soft tissue sample in vitro. The shape parameter of the K- distributed random variable is considered as a statistical marker of temperature level changes. Additionally, the spectral properties of different levels of wavelet approximations are calculated and their sensitivity to temperature increase and decrease is demonstrated. Both approaches registering changes in temperature, are used in the case of the pork loin tissue sample in vitro, heated by an ultrasound beam with a different power.

ultrasound echoes, soft tissue sample in vitro, statistical marker of temperaturę rise

Two heating protocols for soft tissue phantoms have been performed. An Agar-Gel-Oil (AGO) mixture has been heated locally by applying ultrasonic beams and a Poly Vinyl Alcohol-cryogel (PVA-c) has been heated “globally” by a water bath with a controlled temperature rise. The RF signals were collected during heating by an ultrasound transducer to ensure no interference from waves from the heating transducer. Independently, the thermocouples' measurement has been used to obtain temperature as a function of time in the AGO case. At first, a compensation of attenuation was performed and normalized envelopes of signals were used as data for statistical analysis. It is shown that random the values of the backscattered amplitude are close to Rayleigh and K-distributed random variables for AGO and PVA-c, respectively. Temperature is linked to the scale parameter of Rayleigh distribution for the AGO, and the shape parameter of K-distribution for PVA-c were calculated and discussed in the context of their suitability for the acoustic measurement of temperature.

Agar-Gel_Oil soft tissue phantom, K-distribution shape parameter, temperaturę measurements

For the study of the temperature increase in the soft tissues irradiated by a low-power ultrasound [1], soft tissue-mimicking materials can be used. The phantoms have been produced based on an aqueous solution of agar, oil, and glass beads microparticles. The RF signals collected in the experiments enabled evaluation of the acoustic properties of phantoms with different number of strong scatterers (concentration varied from 0 to 30 pcs/mm3). Speed of sound (SOS) determined for the phantoms was similar to the value typical of soft tissue (about 1540 m/s). To determine attenuation coefficient the semi-transmission method has been used. Attenuation coefficient value varied from 0.5 to 1.1 dB/(MHz cm), depending on the number of scatterers. It was shown that the phantoms stored for 6 months preserved their acoustical properties and were usable for further experiments. It was found that within the total attenuation, the part corresponding to scattering can be distinguished.

acoustical characteristics, soft tissue mimicking material, scatterers number

Artykuł dotyczy numerycznego wyznaczania in vivo przestrzennego i czasowego rozkładu temperatury po oddziaływaniu na tkankę zogniskowaną wiązką ultradźwiękową małej mocy. Celem pracy jest analiza wpływu parametrów fizycznych tkanki na rozkład temperatury oraz przedstawienie wyników obliczeń dla modelu wątroby szczura, w którym uwzględniono zależność parametrów fizycznych tkanki od temperatury. Wykazano, że przewidywana temperatura tkanki po 20-minutowym oddziaływaniu w większym stopniu zależy od zmiany przewodnictwa cieplnego tkanki niż od jej ciepła właściwego. Parametry materiałowe wody i tkanki wątroby przyjęto na podstawie danych z literatury. Założono, że geometria modelu numerycznego odpowiada rzeczywistemu położeniu obszaru oddziaływania względem głowicy emitującej zogniskowaną wiązkę ultradźwiękową.

wiązka ultradźwiękowa małej mocy, rozkład temperatury, tkanka miękka, przewodność cieplna, ciepło właściwe

The aim of this work is mathematical modeling and numerical calculation in space and time of temperature fields induced by low power focused ultrasound beams in soft tissue in vivo after few minutes exposure time. These numerical predictions are indispensable for planning of various ultrasound therapeutic applications. Both, the acoustic pressure distribution and power density of heat sources induced in tissue, were calculated using the numerical solution to the second order nonlinear differential wave equation describing propagation of the high intensity acoustic wave in three-layer structure of nonlinear attenuating media. The problem of the heat transfer in living tissues is modelled by the Pennes equation, which accounts for the effects of heat diffusion, blood perfusion losses and metabolism rate. Boundary conditions and geometry are chosen according to the anatomical dimensions of a rat liver. The obtained results are compared with those calculated previously and verified experimentally for temperature elevations induced by ultrasound in liver samples in vitro. The analysis of the results emphasizes the value of the blood perfusion and the values of heat conductivity on the temperature growth rate. The numerical calculations of temperature fields were performed using the ABAQUS FEM software package. The thermal and acoustic properties of the liver and water being the input parameters to the numerical model were taken from the published data in cited references. The range of thermal conductivity coefficient of living tissue is obtained from the model of two-phase composite medium with given microstructure. The first component is a “solid” tissue and the second one corresponds to blood vessels area. The circular focused ultrasonic transducer with a diameter of 15 mm, focal length of 25 mm and resonance frequency of 2 MHz has been used to generate the pulsed ultrasonic beam in a very introductory experiment in vivo, which has been performed. Numerical prediction confirms qualitatively its results.

focused ultrasound, soft tissues, local thermal fields, numerical modelling

Some aspects of FEM modeling of hyperthermia, the procedure of tissue temperature rise above 37 oC inside the living organism, as a treatment modality, are studied. Low intensity focused ultrasound (LIFU) beam has been used as a source of temperature rise in the liver tissue during performed experiments in vitro. The comparison of the FEM model of the corresponding heating process and the experimental results has been presented in [1]. In the paper, the FEM model of heating scheme of the rat liver tissue in vivo irradiated by the same ultrasound transducer is formulated. At first, the existence of blood perfusion is taken into account in the model equation. Secondly, the thermal and acoustical properties, which are the input parameters of the numerical model, are taken from the published data in literature. Here, the size and the intensity of heat sources are modeled in two ways on the basis of acoustic nonlinear equation solutions in 3 layers attenuating medium. We demonstrate how the results of FEM model in the case of in vitro and in vivo heating, depend on the assumed power density of heat sources, as well as on the size of the heated area. The results are compared and discussed. The influence of different models on temperature rise profiles are demonstrated.

The aim of this work is twofold. Firstly, to verify a theoretical model which is capable of predicting temperature fields appearing in soft tissues during their ultrasound treatment. Secondly, to analyze some aspects of the dynamics of Heat Shock Response induced by the heating process in the context of therapeutic treatment. The theoretical investigations and quantitive analysis of temperature increments at any field point versus time of heating process, depending on the heat source power, spatial distribution and duration as well as on the tissue thermal properties, has been carried out by Finite Element Method (FEM). The validation of the numerical model has been performed by comparison of the calculation results with the experimental data obtained by measuring in vitro of the 3D temperature increments induced in samples of the turkey and veal liver by the circular focused transducer with the diameter of 15 mm, focal length of 25 mm and resonance frequency of 2 MHz. Various ultrasonic regimes were considered. They were controlled by adjusting ultrasound power and exposure time. The heat shock proteins (HSP) and misfolded proteins (MFP) levels during the proposed cyclic sonification are presented.

heat-responsive gene therapy, temperature field, low-power focused ultrasound, soft tissues, ultrasonic regime control, heat sources distribution, heat shock proteins

The paper is a review of modern mathematical methods for the analysis of continuous problems of nonlinear mechanics and magnetism. The bibliography contains 175 items. The second part of the paper deals with mechanical problems described by nonconvex density energy functions and with numerical methods to solve such problems.

The aim of the paper was a preliminary comparison of heating efficiency by the two physically different modalities, namely ultrasound sonication and alternating magnetic field, of magnetic nanoparticles added to an agar-gel. Special agar-based tissue mimicking material (TMM) were manufactured from agar with the addition of produced by us iron oxide magnetic nanoparticles of order c/a 11 nanometers. To perform comparison of heating by the measured temperature rise curves caused by the two physical fields differently acting on the material sample, in the case of ultrasonic radiation we did not locate the sensor of thermometer in the ultrasonic beam focus, as it was usually studied, but we put it in the place where distribution of ultrasound intensity was more homogeneous. It was motivated by the fact that the “homogeneous heating” by the magnetic iron oxide nanoparticles which are spatially homogeneously distributed should be compared with the ultrasonic heating effects caused by the spatially homogeneous ultrasonic sources. The obtained results confirm that for both fields, ultrasound and magnetic, the temperature increase was caused by the presence of nanoparticles. In the case of heating by magnetic field pure agar-gel was not heated at all, and during sonication the pure agar-gel exhibited very small thermal effect, due only to the structure of the agar-gel crosslinking. We concluded that the ultrasonic absorption was in our experiment greater than magnetic, but the temperature rise after 180 s of magnetic field action was greater than of sonication.

Heating systems, Ultrasonic imaging, Temperature measurement, Acoustics, Magnetic fields, Nanoparticles, Ultrasonic variables measurement

Agar-gel based materials are widely used as tissue mimicking materials. Pure agar-gel is stable up to 60◦C but exhibits small ultrasound attenuation compared to a soft tissue. To enhance the attenuation of agar-gel we fabricated samples of agar-gel with the adding of graphite micro particles (GMP), magnetic micro particles (MMP) and magnetic nano particles (MNP) with two weight fractions of dry powders added before the formation of the gel to the aqueous agar solution, namely 0.8 % and 1.6 %, respectively. In order to compare the thermal effect caused by the addition of a particles, the samples immersed in a water bath were heated by 2 MHz circular focused transducer (diameter 44 mm), with power of 1, 2, 3 and 4 W. The temperature rise curves were recorded using thermocouples. The temperature change rate (TCR) in the initial point of heating was calculated. For the 0.8 % weight fraction the MMP sample had the highest TCR value at each sound power tested, the smallest value had the MNP sample. For the 1.6 % weight fraction, the highest TCR value had the MNP sample, while the smallest TCR had the GMP sample. We stated that for the higher fraction of particles, the MNP material had the highest TCR value for all powers, and besides the difference between TCR in MMP and GMP samples was less than the difference between TCR in MMP and MNP samples. Besides, the MNP sample exhibited the minimal exposure time to achieve the temperature increment of 5◦C for all applied acoustic powers. These facts underline the unique properties of MNP material and its usefulness as a model material for ultrasonic hyperthermia experiments.

tissue mimicking materials, ultrasound hyperthermia, nano and micro magnetic particles, temperature change rate

The aim of the study was finding the relationship between BIRADS classification combined with envelope K and Nakagami statistics of the echoes backscattered in the breast tissue in vivo and the histological data. 107 breast lesions were examined. Both, the RF echo-signal and B-mode images from the lesions and surrounding tissue were recorded. The analysis method was based on the combining data from BIRADS classifications and both distributions parameters. 107 breasts lesions - 32 malignant and 75 benign - were examined. When only BIRADS classification was used all malignant lesions were diagnosed correctly, however 34 benign lesions were sent for the biopsy unnecessarily. For K distribution the sensitivity and specificity were 78.13%, and 86.67% while for Nakagami statistics the sensitivity and specificity were 62.50% and 93.33%, respectively. Combined K and BIRADS resulted in sensitivity of 96.67% and specificity 60%. Combined BIRADS (3/4a cut-off) plus Nakagami statistics showed 100% of sensitivity with specificity equal 57.33%, decreasing the number of lesions which were biopsied from 34 to 28.

breast cancer, quantitative ultrasound, BIRADS

The work concerns in finding the ultrasonic characteristics of temperature changes within the heated region of two types of samples: phantom sample made from PVA (Polyvinyl Alcohol Cryogel) and soft tissues sample in vitro. We are looking for changes in the statistical parameters of the backscattered signals registered during two different heating procedures for the two types of samples. We are looking for statistical distributions describing the statistics of the signal envelope received during the experiments heating/cooling. Matching of the histogram to the different probability density functions of Rayleigh, Gamma, Nakagami and K-distribution was analyzed by calculating the mean square error. Besides, the dependence on temperature changes of characteristic parameters for considered distributions have been calculated. We conclude that the shape parameter of K-distribution is the best statistical marker of a temperature level in the performed experiments.

therapeutic applications, ultrasonics, medical imaging

Terapeutyczne i chirurgiczne zastosowania ogniskowych ultradźwięków wymagają monitorowania lokalnych zmian temperatury w tkance. Najkorzystniejsze z punktu widzenia użytkowego i ekonomicznego byłoby zastosowanie do tych celów technik ultradźwiękowych.
Praca przedstawia próbę zastosowania metody estymacji przemieszczenia ech do monitorowania zmian temperatury podczas ultradźwiękowego nagrzewania tkanki in vitro. Dane uzyskane drogą pomiarów ultradźwiękowych zostały przetworzone w celu wyznaczenia mapy przemieszczeń ech i odniesione do pomiarów rozkładu temperatury przeprowadzonych za pomocą termopar. Uzyskane wyniki umożliwiają ocenę pola temperatury i pozytywnie rokują połączeniu ultradźwiękowych technik nagrzewania i szacowania lokalnej temperatury tkanki.

obrazowanie temperatury, prędkość akustyczna

W pracy przedstawiono wstępne wyniki pomiaru pola temperatury wewnątrz tkanki in vitro w czasie procesu nagrzewania wiązką ultradźwiękową o słabej mocy oraz pomiaru właściwości akustycznych wzorców tkanek miękkich. Wzorce te zbudowano w celu dalszych badań nad powiązaniem wzrostu temperatury z właściwościami akustycznymi, gdyż próbki tkankowe in vitro okazały się niepowtarzalne i nietrwałe. Na wykonanych 3 wzorcach tkankowych dokonano pomiaru sygnału przejścia i wyznaczono prędkość propagacji impulsu, współczynnik tłumienia oraz zbadano statystykę rozproszenia. Przedyskutowano wpływ liczby elementów rozpraszających na te wielkości.

wzorce tkanek, sygnał ultradźwiękowy, prędkość dźwięku, tłumienie, statystyka rozproszenia

Therapeutic and surgical applications of focused ultrasound require monitoring of local temperature rises induced inside tissues. From an economic and practical point of view ultrasonic imaging techniques seem to be the best for a temperature control. In this work an attempt to apply the method of the ultrasonic echoes displacement estimation for monitoring local temperature rises in tissues during their heating by focused ultrasound is presented. The estimated temperature rise was compared with this measured by a thermocouple. The obtained results enable to evaluate the temperature fields induced in tissues by pulsed focused ultrasonic beams using non-invasive imaging ultrasound technique.

HIFU, therapeutic ultrasound, ultrasonic imaging, echo strain estimation

W pracy rozpatrzono modelowanie hipertermii, to jest procedury podwyższania temperatury powyżej 37 oC w celach terapeutycznych. Skoncentrowana wiązka ultradźwiękowa niskiej mocy była poprzednio wykorzystywana jako źródło ciepła w tkance wątroby w doświadczeniach przeprowadzanych in vitro. Do generowania impulsu wiązki ultradźwiękowej został użyty okrągły skupiający przetwornik piezoelektryczny o średnicy 15 [mm], długości ogniskowej 25 [mm] i częstotliwości rezonansowej 2 [MHz]. Eksperymentalne dane wzrostu temperatury mierzone przez termopary, zostały porównane z wynikami obliczeniowymi otrzymanymi z modelu numerycznego bazującego się na metodzie elementów skończonych. W tej pracy użyto metody elementów skończonych do obliczenia procesu nagrzewania tkanek in vivo. Po pierwsze, w modelowaniu została uwzględniona perfuzja krwi, jako ujemne źródła ciepła zależne liniowo od przyrostu temperatury. Po drugie, właściwości termiczne i akustyczne tkanki używane w modelu numerycznym zastały przyjęte z opublikowanych danych, podczas gdy rozmiar i intensywność źródeł ciepła modelowane są w zgodzie z wynikami uzyskanymi z rozwiązań nieliniowego równania propagacji fali akustycznej w trójwarstwowym ośrodku stratnym. Pokazano, że wyniki modelu numerycznego procesu nagrzewania w tkance in vivo silnie zależą od gęstości mocy cieplnej źródeł oraz od rozmiaru obszaru nagrzewania. Źródła ciepła aproksymowano numeryczne na dwa różne sposoby. Pierwszy, polegał na modelowaniu źródeł ciepła, jako jednorodnego rozkładu gęstości mocy cieplnej rozłożonej w objętości 3 cylindrów imitujących kształt wiązki akustycznej. Drugi sposób przyjmuje ciągły, niejednorodny rozkład gęstości mocy uzyskany bezpośrednio z numerycznego rozwiązania przez odpowiednio dobrane aproksymanty Padé (funkcje wymierne). Wyniki są porównywane i omówione. Pokazano wpływ różnych modeli na profile wzrostu temperatury.

hipotermia, transplantacja nerki, urządzenie do chłodzenia narządów

Lokalna hipertermia, czyli podwyższenie temperatury tkanki w określonym miejscu do temperatury około 44 stopni C, spowodowana absorpcją dostarczonej z zewnątrz energii, jest wykorzystywana np. w leczeniu nowotworów. Hipertermia może być wywołana przez naświetlanie skoncentrowaną wiązką ultradźwiękową lub zmienne pola magnetyczne o określonych mocach i częstotliwościach. Procedury hipertermii powinny być wstępnie kalibrowane na wzorcach tkankowych, czyli na materiałach tkanko-podobnych, aby zapewnić bezpieczeństwo termiczne żywych tkanek. W przypadku hipertermii ultradźwiękowej materiały te powinny posiadać podobne do tkanek właściwości fizyczne, w szczególności powinny w podobny sposób tłumić i rozpraszać ultradźwięki. Najprostsze w przygotowaniu i najczęściej wykorzystywane w doświadczeniach ultradźwiękowych są wzorce na bazie żelu agarowego. Domieszkowanie wzorców agarowych, na przykład, szklanymi kulkami o rozmiarach mikrometrów, jest niezbędne do uzyskanie właściwości akustycznych zbliżonych do właściwości tkanek miękkich. W pracy zbadano wpływ na efektywność hipertermii ultradźwiękowej domieszkowania wzorców agarowych nanocząstkami magnetycznymi w porównaniu do innych cząstek o rozmiarach mikrometrycznych. W tym celu zostały wyprodukowane trzy typy wzorców agarowych: z dodatkiem mikrocząsteczek grafitowych o wymiarach mniejszych niż 20 µm oraz mikro i nanocząstek magnetycznych tlenku żelaza, odpowiednio o rozmiarach 50-100 µm oraz 50-100 nm. Do nagrzewanie wzorców wiązką ultradźwiękową stosowano głowicę ogniskującą o częstotliwości 2.2 MHz z różną mocą sygnału nadawczego od 1W do 4 W. Użyto specjalnie zbudowanego stanowiska pomiarowego, pozwalającego na bardzo precyzyjne ustawienie głowicy i kontrolowanie zmian temperatury wewnątrz wzorca wzdłuż osi wiązki. Rejestracja temperatury w ciągu 5 min naświetlania z częstotliwością co 1 s odbywała się przy użyciu modułu USB-TEMP i 7 termopar. Analiza zarejestrowanych danych pomiarowych pokazała, że najefektywniejszym dodatkiem do agarowych wzorców przy hipertermii ultradźwiękowej wśród badanych typów domieszek są nanocząstki tlenku żelaza. Ich obecność wpływa mocniej na wzrost temperatury podczas działania ultradźwięków, niż obecność domieszek z mikronowych cząstek z tego samego materiału lub grafitu. Obliczono współczynnik absorpcji właściwej (ang. specific absorption rate, SAR), który mierzy efektywność hipertermii. Wartości SAR są najwyższe dla wzorców domieszkowanych nanocząstkami ze wszystkich próbek przy założeniu znajomości ciepła właściwego każdego składnika.

We used 7 types of samples, ”pure agar-gel” sample (AG), agar-gel doped with graphite micro-particles (GMP), agar-gel doped with magnetic micro-particles (MMP) and agar-gel doped with magnetic nanoparticles (MNP) with every doping in two different proportion of ingredients, namely of weigh percentage of 0.8 and 1.6 of the added particles. In the series of experiments we registered RF echoes of backscattered signals emitted by single-element transducer with focus posed on the metal reflector and in the focus posed inside the samples. From this data the speed of sound, the frequency dependent attenuation and backscatternig coefficient were obtained for every sample. Additionally, densities of sample materials were determined, and the elasticity coefficient and acoustical impedance of every material were calculated under the assumption of linear propagation. From the differences between attenuation and scattering the estimation of absorption were performed. The measurements demonstrated that adding the nanoparticles increased the density of the material compare to adding microparticles made from the same magnetic material. The elasticity coefficient and impedance are proportional to the fraction of particles and the elasticity of phantom components. The most interesting conclusion concerns in comparison of difference in ultrasonic absorption. The absorption of agar-gel with NMP exhibited the largest value in between all studied cases. This allows us to assume that the local heating of the medium by the ultrasonic beam should be more efficient in this case, and dopes of iron oxide nanoparticles can be considered as ”sono-sensitizers” in performing ultrasonic hyperthermia. It is worth noting, that this result was independently confirmed by the measuring of temperature rise during the heating of phantoms by the focused ultrasound beams of different powers. This result is presented in another paper at this conference.

Poly(vinyl alcohol) cryogel, PVA-C, is produced as a soft tissue-mimicking material, suitable for application in ultrasound imaging. A 10% by weight poly(vinyl alcohol) in water solution was used to form PVA-C, which is solidified through a freeze–thaw process. The number of freeze–thaw cycles affects the properties of the material, particularly the mechanical stiffness. The ultrasound characteristics were investigated using 3 different cylindrical samples of PVA-C produced by 1, 2 and 3 cycles of freezing-thawing process. The speed of sound was found to range from 1502 to 1522 m s−1, and the attenuation coefficients were in the range of 0.085–0.124 dB/(cm MHz). The structural eterogeneities are visualized by Nakagami maps and it is shown that the range of Nakagami parameter characterize the differences between samples. The samples are structurally different in the regions close to the surface from the internal regions. This is probably caused by the spatial heterogeneity of the solidification process. The thickness of the boundary layer is also measured from Nakagami maps and it is shown that it is also linked to the type of samples. The elastography maps (measured by the commercial quasistatic strain imaging system …) are compared with Nakagami maps. The question arises, in what circumstances parametric estimation of spatial structure variations by Nakagami maps are linked to the spatial variations of local stiffness?

soft tissue phantoms, elastography, ultrasound attenuation, speed of sound, Nakagami maps, stiffness

soft tissue phantoms, backscattered ultrasonic signal, changes in the backscattered energy

After discovery of strong sonar systems, it was realized that the high intensity ultrasound waves can be dangerous for biological organisms. This observation led to research in tissue heating effects. The liver tissue from mathematical point of view can be considered as a micro-periodic cellular medium, and in circumstances justified by biological reasons, the mathematical methods of homogenisation developed for micro-periodic media can be applied to determine some overall properties of the tissue. Fourier’s heat diffusion term in Pennes’ equation is the point of departure in our analysis, [1, 2, 3]. The liver, the largest internal organ in the human body, is connected to two large blood vessels, the hepatic artery and the portal vein. The hepatic artery carries oxygen-rich blood from the aorta, whereas the portal vein carries blood rich in digested nutrients from the entire gastrointestinal tract and also from the spleen and pancreas. These blood vessels subdivide into small capillaries known as liver sinusoids, which then lead to a lobule. A hepatic lobule is a small division of the liver defined at the histological scale. The lobules are arranged into an hexagonal lattice.
We have evaluated the dependence of effective conductivity λeff for the composite consisting of the basic cells arranged in a two-dimensional periodic system and built of the collagen capillaries filled with the water. Analytical and numerical results are going to be verified by measurement of temperature using magnetic resonance imaging (MRI) and through measurement of backscattered ultrasound waves.

liver tissue, Pennes’ equation, heat transport, asymptotic homogenization, effective coefficients

Tissue mimicking materials for ultrasound research, phantoms, should be acousticaly similar to the tissues. Such requirements are filled by the AGO (agar-oil) phantoms. Here, they have been used in experiment of heating internal region of samples by the high intensity ultrasound (HIFU) transducer. During heating the RF (radio frequency) ultrasound signals have been collected. It is demonstrated that the temperature changes in AGO phantoms can be described by the special properties of the backscattered RF signals, namely the shape parameter of the Nakagami distribution and SNR (signal to noise ratio) of signal envelopes random distribution. Reveal of qualitative relationships between the temperature increase/decrease measured by thermocouples and the statistical parameters changes are the main result of the paper.

soft tissue phantom, absorption of acoustic energy, temperature marker, signal-to-noise ratio, Nakagami distribution

A B-mode ultrasonography provides structural information on the tissue under investigation encoding the echo strength in gray scale in a two-dimensional image. Interpretation of the B-mode image of breast tissue is done by a physician. The analysis of statistical properties of backscattered RF signal has been recently applied successfully to distinct healthy tissue from tissue lesions regions as a new method of quantitative ultrasound (QUS). Up till now, the most reliable results were obtained for liver and renal tissue lesions, because their normal, healthy structures are nearly homogeneous while a heterogeneous breast tissue classification is still an open issue. The recent study revealed that the medium contraction and expansion induced by a temperature change may cause variations in the relative position of scatterers in a tissue. We have developed a new procedure of heating the patient breast and allowing to observe and record in vivo the influence of temperature changes on a B-mode image and properties of unprocessed radio frequency (RF) backscattered echoes. The initial, feasibility studies of influence of the temperature increase in breast tissue on the intensity, spectrum and statistics of ultrasonic echoes will be discussed.

breast tissue, RF signal, backscattered signal amplitude statistics, spectral properties

For the study of the temperature increase in the soft tissues irradiated by a lowpower ultrasound, see [1], soft tissue phantoms can be used. They should exhibit acoustic properties similar to soft tissue and being sufficiently stable during the hyperthermia treatment. Such phantoms have been produced based on an aqueous solution of agar, oil, and glass microparticles. The FR signals collected in experiments provide to obtain the acoustic properties of phantoms with different numbers of scatterers, from 0-30/mm3. Measured ultrasonic wave velocity in the phantoms is similar to the typical velocity in soft tissues and is equal about 1540 m / s. Attenuation coefficient has been determined by two methods - the pulse method, and the spectral shift method. It is changed in the range of 0.5 to 1.1 dB / (MHz cm), depending on the number of scatterers. It was verified that the patterns do not alter the parameters during 6 months in suitable conditions of storage after production and can be used for further experiments. Besides, based on the analysis of the backscattered signal from pulse/echo ultrasound the statistical properties of the signal envelope and the attenuation coefficient have been studied. It was found that within the total attenuation, the part can be distinguished corresponding to the attenuation due to Rayleigh scattering.

lowpower ultrasound, scatterers number,attenuation, Rayleigh scattering