Structural, Magnetic and Heating Efficiency of Ball Milled γ-Fe2O3/Gd2O3 Nanocomposite for Magnetic Hyperthermia

The preparation of γ-Fe2O3/Gd2O3 nanocomposite for possible use in magnetic hyperthermia application was done by ball milling technique. The nanocomposite was characterized by X-ray diffraction (XRD) and vibrating sample magnetometer (VSM). The heating efficiency and the effect of milling time (5 h and 30 h) on the structural and magnetic properties of the nanocomposite were reported. XRD analysis confirms the formation of the nanocomposite, while magnetization measurements show that the milled sample present hysteresis with low coercivity and remanence. The specific absorption rate (SAR) under an alternating magnetic field is investigated as a function of the milling time. A mean heating efficiency of 68 W/g and 28.7 W/g are obtained for 5 h and 30 h milling times respectively at 332 kHz and 170 Oe. The results showed that the obtained nanocomposite for 5 h milling time is a promising candidate for magnetic hyperthermia due to his properties which show an interesting magnetic behavior and high specific absorption rate.

Extraction method of nanoparticles concentration distribution from magnetic particle image and its application in thermal damage of magnetic hyperthermia

Magnetic particle imaging(MPI)technology can generate a real-time magnetic nanoparticle(MNP)distribution image for biological tissues,and its use can overcome the limitations imposed in magnetic hyperthermia treatments by the unpredictable MNP distribution after the intratumoral injection of nanofluid.However,the MNP concentration distribution is generally difficult to be extracted from MPI images.This study proposes an approach to extract the corresponding concentration value of each pixel from an MPI image by a least squares method(LSM),which is then translated as MNP concentration distribution by an interpolation function.The resulting MPI-based concentration distribution is used to evaluate the treatment effect and the results are compared with the ones of two baseline cases under the same dose:uniform distribution and MPI-based distribution considering diffusion.Additionally,the treatment effect for all these cases is affected by the blood perfusion rate,which is also investigated deeply in this study.The results demonstrate that the proposed method can be used to effectively reconstruct the concentration distribution from MPI images,and that the weighted LSM considering a quartic polynomial for interpolation provides the best results with respect to other cases considered.Furthermore,the results show that the uniformity of MNP distribution has a positive correlation with both therapeutic temperature distribution and thermal damage degree for the same dose and a critical power dissipation value in the MNPs.The MNPs uniformity inside biological tissue can be improved by the diffusion behavior after the nanofluid injection,which can ultimately reflect as an improvement of treatment effect.In addition,the blood perfusion rate considering local temperature can have a positive effect on the treatment compared to the case which considers a constant value during magnetic hyperthermia.

Physical Interpretation of Electricity and Magnetism and Electromagnetic Induction

Electricity and magnetism and electromagnetic induction are phenomena that can be perceived by people. But their interpretation and theoretical study took a long time. The theoretical research on electricity began with the discovery of Coulomb’s law in 1785, while the theoretical research on magnetism began with the discovery of Oersted’s Law in 1820. From the 1850s to the 1870s, Maxwell summarized a set of theoretical equations for electromagnetism based on some laws of predecessors. However, this set of equations contains a few statistical relationships and empirical concepts, so it is difficult to explain the physical nature of electromagnetic phenomena and principles. This paper explained that the macro phenomenon of electricity is the separation of unlike charges of new electrons produced by the orthogonal collision of old particles under the action of external forces. The physical nature of magnetism is the potential energy (magnetic energy) and information associated with the overall orientation of the moving electrons solidly recorded in the material. The physical principle of electromagnetic induction describes how change in electric current intensity generates change in magnetic intensity and vice versa through orthogonal interaction of ordered electrons. This theoretical interpretation does not require the concepts of traditional electromagnetic forces, electromagnetic fields, magnetic moments, and magnetic domains.

Magnetic-mediated hyperthermia for cancer treatment:Research progress and clinical trials

Research progress and frontiers of magnetic-mediated hyperthermia （MMH） are presented, along with clinical trials in Germany, the US, Japan, and China. Special attention is focused on MMH mediated by magnetic nanoparticles, and multifunctional magnetic devices for cancer multimodality treatment are also introduced.

Acoustic dipole radiation model for magnetoacoustic tomography with magnetic induction

An acoustic dipole radiation model for magnetoacoustic tomography with magnetic induction （MAT-MI） is pro- posed, based on the analyses of one-dimensional tissue vibration, three-dimensional acoustic dipole radiation and acoustic waveform detection with a planar piston transducer. The collected waveforms provide information about the conductiv- ity boundaries in various vibration intensities and phases due to the acoustic dipole radiation pattern. Combined with the simplified back projection algorithm, the conductivity configuration of the measured layer in terms of shape and size can be reconstructed with obvious border stripes. The numerical simulation is performed for a two-layer cylindrical phantom model and it is also verified by the experimental results of MAT-MI for a tissue-like sample phantom. The proposed model suggests a potential application of conductivity differentiation and provides a universal basis for the further study of conductivity reconstruction for MAT-MI.

Simulation research on effect of magnetic nanoparticles on physical process of magneto–acoustic tomography with magnetic induction

Magneto–acoustic tomography with magnetic induction（MAT-MI） is a multiphysics coupled imaging technique that is combined with electrical impedance tomography and ultrasound imaging. In order to study the influence of adding magnetic nanoparticles as a contrast agent for MAT-MI on its physical process, firstly, we analyze and compare the electromagnetic and acoustical properties of MAT-MI theoretically before and after adding magnetic nanoparticles, and then construct a two-dimensional（2 D） planar model. Under the guidance of space-time separation theory, we determine the reasonable simulation conditions and solve the electromagnetic field and sound field physical processes in the two modes by using the finite element method. The magnetic flux density, sound pressure distribution, and related one-dimensional（1 D）, 2 D, and three-dimensional（3 D） images are obtained. Finally, we make a qualitative and quantitative analysis based on the theoretical and simulation results. The research results show that the peak time of the time item separated from the sound source has a corresponding relationship with the peak time of the sound pressure signal. At this moment, MAMPTMI produces larger sound pressure signals, and the sound pressure distribution of the MAMPT-MI is more uniform, which facilitates the detection and completion of sound source reconstruction. The research results may lay the foundation for the MAT-MI of magnetically responsive nanoparticle in subsequent experiments and even clinical applications.

Reception pattern influence on magnetoacoustic tomography with magnetic induction

Based on the acoustic radiation theory of a dipole source, the influence of the transducer reception pattern is studied for magnetoacoustic tomography with magnetic induction（MAT-MI）. Numerical studies are conducted to simulate acoustic pressures, waveforms, and reconstructed images with unidirectional, omnidirectional, and strong directional transducers.With the analyses of equivalent and projection sources, the influences of the model dimension and the layer effect are qualitatively analyzed to evaluate the performance of MAT-MI. Three-dimensional simulation studies show that the strong directional transducer with a large radius can reduce the influences of equivalent sources, projection sources, and the layer effect effectively, resulting in enhanced pressure and improved image contrast, which is beneficial for boundary pressure extraction in conductivity reconstruction. The reconstructed conductivity contrast images present the conductivity boundaries as stripes with different contrasts and polarities, representing the values and directions of the conductivity changes of the scanned layer. The favorable results provide solid evidence for transducer selection and suggest potential practical applications of MAT-MI in biomedical imaging.

A thermo-fluid analysis in magnetic hyperthermia

In the last years, hyperthermia induced by the heating of magnetic nanoparticles （MNPs） in an alternating magnetic field received considerable attention in cancer therapy. The thermal effects could be automatically controlled by using MNPs with selective magnetic absorption properties. In this paper, we analyze the temperature field determined by the heating of MNPs, injected in a malignant tissue, subjected to an alternating magnetic field. The main parameters which have a strong influence on temperature field are analyzed. The temperature evolution within healthy and tumor tissues are analyzed by finite element method （FEM） simulations in a thermo-fluid model. The cooling effect produced by blood flow in blood vessels from the tumor is considered. A thermal analysis is conducted under different distributions of MNP injection sites. The interdependence between the optimum dose of the nanoparticles and various types of tumors is investigated in order to understand their thermal effect on hyperthermia therapy. The control of the temperature field in the tumor and healthy tissues is an important step in the healing treatment.

Usefulness of Magnetic Particle Imaging for Predicting the Therapeutic Effect of Magnetic Hyperthermia

Purpose: To investigate the usefulness of magnetic particle imaging (MPI) for predicting the therapeutic effect of magnetic hyperthermia (MH). Materials and Methods: First, we performed phantom experiments to investigate the relationship between the MPI value and the temperature rise of magnetic nanoparticles (MNPs) under an alternating magnetic field (AMF). The MPI value was defined as the pixel value of the transverse image reconstructed from the third-harmonic signals. Samples filled with various iron concentrations of MNPs (Resovist®) were prepared and were imaged using our MPI scanner. These samples were also heated using the AMF, and the specific loss power (SLP) and volume-specific loss power (vSLP) were calculated from the initial slope of the time-dependent temperature rise. Second, we performed animal experiments using tumor-bearing mice, which were divided into untreated (n = 10) and treated groups (n = 20). The tumors in the treated group were injected with Resovist®?at an iron concentration of 250 mM (n = 10) or 500 mM (n = 10), and received MH for 20 min, during which the temperatures in the tumor and rectum were measured. The relative tumor volume growth (RTVG) was calculated from (V15 -?V0)/V0, where V0 and V15 represented the tumor volume on day 0 and day 15 after MH, respectively. Results: In phantom experiments, the MPI value had significant correlations with the iron concentration of MNPs (r = 0.997), temperature rise (r = 0.981), and vSLP (r = 0.961). In animal experiments, the MPI value had significant correlations with the temperature rise in the tumor (r = 0.731) and RTVG (r = ﹣0.687). Conclusion: Our preliminary results suggest that MPI is useful for predicting the therapeutic effect of MH.

Boundary normal pressure-based electrical conductivity reconstruction for magneto–acoustic tomography with magnetic induction

As a kind of multi-physics imaging approach integrating the advantages of electrical impedance tomography and ul- trasound imaging with the improved spatial resolution and image contrast, magneto-acoustic tomography with magnetic induction （MAT-MI） is demonstrated to have the capability of electrical impedance contrast imaging for biological tissues with conductivity differences. By being detected with a strong directional transducer, abrupt pressure change is proved to be generated by the gradient of the induced Lorentz force along the force direction at conductivity boundary. A simplified boundary normal pressure （BNP）-based conductivity reconstruction algorithm is proposed and the formula for conductivity distribution inside the object with the clear physical meaning of pressure derivative, is derived. Numerical simulations of acoustic pressure and conductivity reconstruction are conducted based on a 2-layer eccentric cylindrical phantom model using Hilbert transform. The reconstructed two-dimensional conductivity images accord well with the model, thus success- fully making up the deficiency of only imaging conductivity boundary in traditional MAT-MI. The proposed method is also demonstrated to have a spatial resolution of one wavelength. This study provides a new method of reconstructing accurate electrical conductivity and suggests the potential applications of MAT-MI in imaging biological tissues with conductivity difference.

Magnetic Particle Imaging for Magnetic Hyperthermia Treatment: Visualization and Quantification of the Intratumoral Distribution and Temporal Change of Magnetic Nanoparticles in Vivo

Purpose: Magnetic hyperthermia treatment (MHT) is a strategy for cancer therapy using the tem-perature rise of magnetic nanoparticles (MNPs) under an alternating magnetic field (AMF). Re-cently, a new imaging method called magnetic particle imaging (MPI) has been introduced. MPI allows imaging of the spatial distribution of MNPs. The purpose of this study was to investigate the feasibility of visualizing and quantifying the intratumoral distribution and temporal change of MNPs and predicting the therapeutic effect of MHT using MPI. Materials and Methods: Colon-26 cells (1 × 106 cells) were implanted into the backs of eight-week-old male BALB/c mice. When the tumor volume reached approximately 100 mm3, mice were divided into untreated (n = 10) and treated groups (n = 27). The tumors in the treated group were directly injected with MNPs (Resovist?) with iron concentrations of 500 mM (A, n = 9), 400 mM (B, n = 8), and 250 mM (C, n = 10), respectively, and MHT was performed using an AMF with a frequency of 600 kHz and a peak amplitude of 3.5 kA/m. The mice in the treated group were scanned using our MPI scanner immediately before, immediately after, 7 days, and 14 days after MHT. We drew a region of interest (ROI) on the tumor in the MPI image and calculated the average, maximum, and total MPI values and the number of pixels by taking the threshold value for extracting the contour as 40% of the maximum MPI value (pixel value) within the ROI. These parameters in the untreated group were taken as zero. We also measured the relative tumor volume growth (RTVG) defined by (V-V0)/V0, where V0 and V are the tumor volumes immediately before and after MHT, respectively. Results: The average, maximum, and total MPI values decreased up to 7 days after MHT and remained almost constant thereafter in all groups, whereas the number of pixels tended to increase with time. The RTVG values in Groups A and B were significantly lower than those in the control group 3 days or more and 5 days or more after MHT, respectively. The above four parameters were significantly inversely correlated with the RTVG values 5, 7, and 14 days after MHT. Conclusion: MPI can visualize and quantify the intratumoral distribution and temporal change of MNPs before and after MHT. Our results suggest that MPI will be useful for predicting the therapeutic effect of MHT and for the treatment planning of MHT.

Magnetometry and Hyperthermia Study of Magnetic Fluid Preparation UNIMAG

We investigated the hyperthermal and magnetic properties of the stable magnetic suspension of magnetite nanoparticles. With this purpose in mind, we designed a low-frequency oscillator, 300 W, 300 KHz. A sample of the magnetic suspension was placed in the induction coil and heated up to 55°C for 30 minutes. Based on the results of measurements of transverse susceptibility, we can infer that the suspension was superparamagnetic at room temperature and transformed into the magnetic state at nitrogen temperature. Comparing the obtained experimental results with the literature data, we assessed the mean size of nanoparticles, which made up about 10 nm. Computer simulation assessment on the basis of magnetization curve gives close results.

Bovine Serum Albumin-Conjugated Ferrimagnetic Iron Oxide Nanoparticles to Enhance the Biocompatibility and Magnetic Hyperthermia Performance

Magnetic hyperthermia is a fast emerging, non-invasive cancer treatment method which is used synergistically with the existing cancer therapeutics. We have attempted to address the current challenges in clinical magnetic hyperthermia-improved biocompatibility and enhanced heating characteristics, through a single combinatorial approach. Both superparamagnetic iron oxide nanoparticles(SPIONs) of size 10 nm and ferrimagnetic iron oxide nanoparticles(FIONs) of size 30 nm were synthesized by thermal decomposition method for comparison studies. Two different surface modifying agents, viz, Cetyl Trimethyl Ammonium Bromide and 3-Aminopropyltrimethoxysilane, were used to conjugate Bovine Serum Albumin(BSA) over the iron oxide nanoparticles via two different methods—surface charge adsorption and covalent amide bonding, respectively. The preliminary haemolysis and cell viability experiments show that BSA conjugation mitigates the haemolytic effect of the iron oxide nanoparticles on erythrocytes and is non-cytotoxic to the healthy Baby Hamster Kidney cells. It was observed from the results that due to better colloidal stability, the SAR value of the BSA-iron oxide nanoparticles is higher than the iron oxide nanoparticles without BSA, irrespective of the size of the iron oxide nanoparticles and method of conjugation. The BSA-FIONs seem to show improved biocompatibility, as the haemolytic index is less than 2 % and cell viability is up to 120 %, when normalized with the control. The SAR value of BSAFIONs is 2300 Wg^(-1) when compared to 1700 Wg^(-1) of FIONs without BSA conjugation. Thus, we report here that BSA conjugation over FIONs(with a high saturation magnetization of 87 emug^(-1)) provide a single combinatorial approach to improve the biocompatibility and enhance the SAR value for magnetic hyperthermia, thus addressing both the current challenges of the same.

Effects of dipolar interactions on the magnetic hyperthermia of Zn_(0.3)Fe_(2.7)O_(4) nanoparticles with different sizes

Tumor-targeted magnetic hyperthermia has recently attracted much attention.Magnetic nanoparticles(NPs) are heat mediator nanoprobes in magnetic hyperthermia for cancer treatment.In this paper,single cubic spinel structural Zn_(0.3)Fe_(2.7)O_(4) magnetic NPs with sizes of 14 nm-20 nm were synthesized,followed by coating with SiO_(2) shell.The SLP value of Zn_(0.3)Fe_(2.7)O_(4)/SiO_(2) NPs below 20 nm changes non-monotonically with the concentration of solution under the alternating current(AC) magnetic field of 430 kHz and 27 kA/m.SLP values of all Zn_(0.3)Fe_(2.7)O_(4)/SiO_(2) NPs appear a peak value with change of solution concentration.The solution concentrations with optimal SLP value decrease with increasing magnetic core size.This work can give guidance to the better prediction and control of the magnetic hyperthermia performance of materials in clinical applications.

Enhanced hyperthermia performance in hard-soft magnetic mixed Zn0.5CoxFe2.5−xO4/SiO2 composite magnetic nanoparticles

High quality Zn0.5CoxFe2.5−xO4(x=0,0.05,0.1,0.15)serial magnetic nanoparticles with single cubic structures were prepared by the modified thermal decomposition method,and Zn0.5CoxFe2.5−xO4/SiO2 composite magnetic nanoparticles were prepared by surface modification of SiO2.The magnetic anisotropy of the sample increases with the increase of the doping amount of Co2+.When the doping amount is 0.1,the sample shows the transition from superparamagnetism to ferrimagnetism at room temperature.In the Zn0.5CoxFe2.5−xO4/SiO2 serial samples,the maximum value of specific loss power(SLP)with 1974 W/gmetal can also be found at doping amount of x=0.1.The composite nanoparticles are expected to be an excellent candidate for clinical magnetic hyperthermia.

Controlled Local Hyperthermia and Magnetic Hyperthermia of Surface (Skin) Cancer Diseases

Average size of hematite and magnetite micro and nanopowders and polydispersity index, zeta potential and distribution of particles were studied. Analysis showed that average size of the obtained particles for magnetite is 740.9 nm, for hematite particles 30 - 35 nm. Alternate current feed source was created for hyperthermia. Proceeding from the requirements of the objectives, the U type MnZn material magneto conductors were selected, in which 10.0 and 8.0 mm width gaps were cut and glass test tubes with magnetite or hematite suspensions were placed in them. Series of experiments at various field intensity and frequencies showed that for efficient magnetic hyperthermia therapy more powerful device was needed with frequency of up to 10 Mega Hertz to achieve the temperature 43°C - 45°C necessary for full activation of Neel and Brown mechanisms in particles. At the next stage, on the basis of experimental material the anticancer mono-therapeutic effect of hyperthermia and its adjuvant action in poly chemotherapeutic treatment was presented by the use of a device created by us “Lezi”. As a result of the experiment it was shown that in all animals (outbred albino mice, 3 months old) inhibition of cancer growth was fixed and intratumoral necrosis was developed, while after 7 and 10 sessions tumors were ulcerated, which refers to positive effect of the experiment (Conclusion of Pathologicanatomical Laboratory “PATGEO”, Tbilisi, Georgia ).

Thermal apoptosis analysis considering injection behavior optimization and mass diffusion during magnetic hyperthermia

Thermally induced apoptosis for tumors depends mainly on the intrinsic characteristics of biological tissues as well as treatment temperature profile during magnetic hyperthermia.Further,treatment temperature distribution inside tumor depends on the injection behavior of irregular tumors,such as the injection dose and the injection location of nanofluids.In order to improve the treatment effect,the simulated annealing algorithm is adopted in this work to optimize the nanofluid injection behavior,and the improved Arrhenius model is used to evaluate the malignant ablations for three typical malignant tumor cell models.In addition,both the injection behavior optimization and the mass diffusion of nanofluid are both taken into consideration in order to improve the treatment effect.The simulation results demonstrate that the injection behavior can be optimized effectively by the proposed optimization method before therapy,the result of which can also conduce to improving the thermal apoptosis possibility for proposed typical malignant cells.Furthermore,an effective approach is also employed by considering longer diffusion duration and correct power dissipation at the same time.The results show that a better result can then be obtained than those in other cases when the power dissipation of MNPs is set to be QMNP=5.4×10^(7)W·m^(3) and the diffusion time is 16 h.

Hierarchical lichee-like Fe_(3)O_(4) assemblies and their high heating efficiency in magnetic hyperthermia

A nontoxic and biocompatible thermoseed is developed for the magnetic hyperthermia.Two kinds of thermoseed materials:hierarchical hollow and solid lichee-like Fe_(3)O_(4) assemblies,are synthesized by a facile hydrothermal method.The crystal structure of Fe_(3)O_(4) assemblies are characterized by x-ray diffraction,scanning electron microscopy,and transmission electron microscopy.Moreover,the prepared Fe_(3)O_(4) assemblies are used as a magnetic heat treatment agent,and their heating efficiency is investigated.Compared to solid assembly,hollow lichee-like Fe_(3)O_(4) assembly exhibits a higher specific absorption rate of 116.53 W/g and a shorter heating time,which is ascribed to its higher saturation magnetization,larger initial particle size,and the unique hierarchical hollow structure.Furthermore,the magnetothermal effect is primarily attributed to Neel relaxation.Overall,we propose a facile and convenient approach to enhance the heating efficiency of magnetic nanoparticles by forming hollow hierarchical assemblies.

Comparative Study of Extracellular and Intracellular Magnetic Hyperthermia Treatments Using Magnetic Particle Imaging

The purpose of this study was to evaluate the effectiveness of intracellular magnetic hyperthermia treatment (MHT) in comparison with that of extracellular MHT using magnetic particle imaging (MPI). Colon-26 cells were implanted subcutaneously into the backs of 8-week-old male BALB/c mice. When the tumor volume reached approximately 100 mm3, the mice were divided into control (n = 10), extracellular MHT (n = 8), and intracellular MHT groups (n = 7). In the control group, MHT was not performed. In the extracellular MHT and intracellular MHT groups, the tumors were injected directly with magnetic nanoparticles (MNPs) (400 mM Resovist®) and were heated for 20 min using an alternating magnetic field. During MHT, the temperatures of the tumor and rectum were measured using optical fiber thermometers. In the extracellular MHT group, MHT was performed 15 min after the injection of MNPs, whereas MHT was performed one day after the injection of MNPs in the intracellular MHT group. In both groups, MPI images were obtained using our MPI scanner immediately before, immediately after, and 7 and 14 days after MHT. After the MPI studies, we drew a region of interest (ROI) on the tumor in the MPI image and calculated the average, maximum, and total MPI values and the number of pixels within the ROI. Transmission electron microscopic (TEM) images were also obtained from resected tumors. In all groups, tumor volume was measured every day and the relative tumor volume growth (RTVG) was calculated. The TEM images showed that almost all the MNPs were aggregated in the extracellular space in the extracellular MHT group, whereas they were contained within the intracellular space in the intracellular MHT group. Although the temperature of the tumor in the intracellular MHT group was significantly lower than that in the extracellular MHT group, the RTVG value in the intracellular MHT group was significantly lower than that in the control group 2 days or more after MHT and that in the extracellular MHT group 3, 4, and 5 days after MHT. The average MPI value normalized by that immediately before MHT in the intracellular MHT group was significantly higher than that in the extracellular MHT group immediately and 7 days after MHT. The maximum and total MPI values normalized by those immediately before MHT in the intracellular MHT group were significantly higher than those in the extracellular MHT group 7 days after MHT, suggesting that the temporal change of MNPs within the tumor in the intracellular MHT group was smaller than that in the extracellular MHT group. Our results suggest that intracellular MHT is more cytotoxic than extracellular MHT in spite of a lower temperature rise of tumors, and that MPI is useful for evaluating the difference in the temporal change of MNPs in the tumor between extracellular MHT and intracellular MHT.

THE THERMAL EFFECT OF FERRIMAGNETIC RESONANCE AND ITS PROBABLE APPLICATION IN MICROWAVE HYPERTHERMIA IN CANCER THERAPY

To improve microwave hyperthevmia in cancer therapy, the thermal effect of fer-rimagnetic resonance (FMR) during microwave irradiation was studied. Resonant temperatureelevation (RTE) of single crystal grain and polycrystal powder of resonant media was measuredalone and in imitative muscle and egg white and in mice. The results indicated that the RTE produced by FMR could be used to improve penetrationdeepness, heating selectivity and temperature distribution of microwave hyperthermia in cancertreatment. It was expected that the potential function of the FMR heating system would be ex-ploited greatly for cancer therapy, and then magnetically guided microwave hyperthermia thera-py, chemotherapy, radiotherapy and immunotherapy might he combined multiply within this sys-tem by means of the static magnetic field (SMF) and magnetic microcarrier. Limitation of reso-nant heating was also discussed in this paper.