A prediction model for magnetic particle imaging-based magnetic hyperthermia applied to a brain tumor model.

BACKGROUND AND OBJECTIVE: Brain tumor is a global health concern at the moment. Thus far, the only treatments available are radiotherapy and chemotherapy, which have several drawbacks such as low survival rates and low treatment efficacy due to obstruction of the blood-brain barrier. Magnetic hyperthermia (MH) using magnetic nanoparticles (MNPs) is a promising non-invasive approach that has the potential for tumor treatment in deep tissues. Due to the limitations of the current drug-targeting systems, only a small proportion of the injected MNPs can be delivered to the desired area and the rest are distributed throughout the body. Thus, the application of conventional MH can lead to damage to healthy tissues. METHODS: Magnetic particle imaging (MPI)-guided treatment platform for MH is an emerging approach that can be used for spatial localization of MH to arbitrarily selected regions by using the MPI magnetic field gradient. Although the feasibility of this method has been demonstrated experimentally, a multidimensional prediction model, which is of crucial importance for treatment planning, has not yet been developed. Hence, in this study, the time dependent magnetization equation derived by Martsenyuk, Raikher, and Shliomis (which is a macroscopic equation of motion derived from the Fokker-Planck equation for particles with Brownian relaxation mechanism) and the bio-heat equations have been used to develop and investigate a three-dimensional model that predicts specific loss power (SLP), its spatio-thermal resolution (temperature distribution), and the fraction of damage in brain tumors. RESULTS: Based on the simulation results, the spatio-thermal resolution in focused heating depends, in a complex manner, on several parameters ranging from MNPs properties to magnetic fields characteristics, and coils configuration. However, to achieve a high performance in focused heating, the direction and the relative amplitude of the AC magnetic heating field with respect to the magnetic field gradient are among the most important parameters that need to be optimized. The temperature distribution and fraction of the damage in a simple brain model bearing a tumor were also obtained. CONCLUSIONS: The complexity in the relationship between the MNPs properties and fields parameter imposes a trade-off between the heating efficiency of MNPs and the accuracy (resolution) of the focused heating. Therefore, the system configuration and field parameters should be chosen carefully for each specific treatment scenario. In future, the results of the model are expected to lead to the development of an MPI-guided MH treatment platform for brain tumor therapy. However, for more accurate quantitative results in such a platform, a magnetization dynamics model that takes into account coupled Néel-Brownian relaxation mechanism in the MNPs should be developed.

From Low to High Saturation Magnetization in Magnetite Nanoparticles: The Crucial Role of the Molar Ratios Between the Chemicals.

In this study, a comprehensive characterization of iron oxide nanoparticles synthesized by using a simple one-pot thermal decomposition route is presented. In order to obtain monodisperse magnetite nanoparticles with high saturation magnetization, close to the bulk material, the molar ratios between the starting materials (solvents, reducing agents, and surfactants) were varied. Two out of nine conditions investigated in this study resulted in monodisperse iron oxide nanoparticles with high saturation magnetization (90 and 93% of bulk magnetite). The X-ray diffraction analyses along with the inspection of the lattice structure through transmission electron micrographs revealed that the main cause of the reduced magnetization in the other seven samples is likely due to the presence of distortion and microstrain in the particles. Although the thermogravimetric analysis, Raman and Fourier transform infrared spectroscopies confirmed the presence of covalently bonded oleic acid on the surface of all the samples, the particles with higher polydispersity and the lowest surface coating molecules showed the lowest saturation magnetization. Based on the observed results, it could be speculated that the changes in the kinetics of the reactions, induced by varying the molar ratio of the starting chemicals, can lead to the production of the particles with higher polydispersity and/or lattice deformation in their crystal structures. Finally, it was concluded that the experimental conditions for obtaining high-quality iron oxide nanoparticles, particularly the molar ratios and the heating profile, should not be chosen independently; for any specific molar ratio, there may exist a specific heating profile or vice versa. Because this synthetic consideration has rarely been reported in the literature, our results can give insights into the design of iron oxide nanoparticles with high saturation magnetization for different applications.

Highly Optimized Iron Oxide Embedded Poly(Lactic Acid) Nanocomposites for Effective Magnetic Hyperthermia and Biosecurity.

INTRODUCTION: Iron oxide magnetic nanoparticles (IONPs) have attracted considerable attention for various biomedical applications owing to their ease of synthesis, strong magnetic properties, and biocompatibility. In particular, IONPs can generate heat under an alternating magnetic field, the effects of which have been extensively studied for magnetic hyperthermia therapy. However, the development of IONPs with high heating efficiency, biocompatibility, and colloidal stability in physiological environments is still required for their safe and effective application in biomedical fields. METHODS: We synthesized magnetic IONP/polymer nanocomposites (MNCs) by embedding IONPs in a poly(L-lactic acid) (PLA) matrix via nanoemulsion. The IONP contents (Fe: 9-22 [w/w]%) in MNCs were varied to investigate their effects on the magnetic and hyperthermia performances based on their optimal interparticle interactions. Further, we explored the stability, cytocompatibility, biodistribution, and in vivo tissue compatibility of the MNCs. RESULTS: The MNCs showed enhanced heating efficiency with over two-fold increase compared to nonembedded bare IONPs. The relationship between the IONP content and heating performance in MNCs was nonmonotonous. The highest heating performance was obtained from MNC2, which contain 13% Fe (w/w), implying that interparticle interactions in MNCs can be optimized to achieve high heating performance. In addition, the MNCs exhibited good colloidal stability under physiological conditions and maintained their heating efficiency during 48 h of incubation in cell culture medium. Both in vitro and in vivo studies revealed excellent biocompatibility of the MNC. CONCLUSION: Our nanocomposites, comprising biocompatible IONPs and PLA, display improved heating efficiency, good colloidal stability, and cytocompatibility, and thus will be beneficial for diverse biomedical applications, including magnetic hyperthermia for cancer treatment.

Theoretical Analysis for Using Pulsed Heating Power in Magnetic Hyperthermia Therapy of Breast Cancer.

In magnetic hyperthermia, magnetic nanoparticles (MNPs) are used to generate heat in an alternating magnetic field to destroy cancerous cells. This field can be continuous or pulsed. Although a large amount of research has been devoted to studying the efficiency and side effects of continuous fields, little attention has been paid to the use of pulsed fields. In this simulation study, Fourier's law and COMSOL software have been utilized to identify the heating power necessary for treating breast cancer under blood flow and metabolism to obtain the optimized condition among the pulsed powers for thermal ablation. The results showed that for small source diameters (not larger than 4 mm), pulsed powers with high duties were more effective than continuous power. Although by increasing the source domain the fraction of damage caused by continuous power reached the damage caused by the pulsed powers, it affected the healthy tissues more (at least two times greater) than the pulsed powers. Pulsed powers with high duty (0.8 and 0.9) showed the optimized condition and the results have been explained based on the Arrhenius equation. Utilizing the pulsed powers for breast cancer treatment can potentially be an efficient approach for treating breast tumors due to requiring lower heating power and minimizing side effects to the healthy tissues.

Biomimetic phantom with anatomical accuracy for evaluating brain volumetric measurements with magnetic resonance imaging.

Purpose: Brain image volumetric measurements (BVM) methods have been used to quantify brain tissue volumes using magnetic resonance imaging (MRI) when investigating abnormalities. Although BVM methods are widely used, they need to be evaluated to quantify their reliability. Currently, the gold-standard reference to evaluate a BVM is usually manual labeling measurement. Manual volume labeling is a time-consuming and expensive task, but the confidence level ascribed to this method is not absolute. We describe and evaluate a biomimetic brain phantom as an alternative for the manual validation of BVM. Methods: We printed a three-dimensional (3D) brain mold using an MRI of a three-year-old boy diagnosed with Sturge-Weber syndrome. Then we prepared three different mixtures of styrene-ethylene/butylene-styrene gel and paraffin to mimic white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF). The mold was filled by these three mixtures with known volumes. We scanned the brain phantom using two MRI scanners, 1.5 and 3.0 Tesla. Our suggestion is a new challenging model to evaluate the BVM which includes the measured volumes of the phantom compartments and its MRI. We investigated the performance of an automatic BVM, i.e., the expectation-maximization (EM) method, to estimate its accuracy in BVM. Results: The automatic BVM results using the EM method showed a relative error (regarding the phantom volume) of 0.08, 0.03, and 0.13 ( ± 0.03 uncertainty) percentages of the GM, CSF, and WM volume, respectively, which was in good agreement with the results reported using manual segmentation. Conclusions: The phantom can be a potential quantifier for a wide range of segmentation methods.

A Novel Theranostic Platform: Integration of Magnetomotive and Thermal Ultrasound Imaging With Magnetic Hyperthermia.

OBJECTIVE: Nanotheranostic systems integrate therapeutic and diagnostic procedures using nanotechnology. This type of approach has enabled the development of methods for early detection and treatment of different pathologies. Magnetic hyperthermia (MH) has been proposed as an alternative or complementary method of cancer therapy. However, challenges such as delivering and localizing the magnetic nanoparticles (MNPs) within tissues and monitoring the temperature during the treatment hinder this technique to be effectively translated into a clinical routine. Therefore, in this study a theranostic platform has been proposed and examined to address two main issues, localizing MNPs and real-time temperature monitoring, for preclinical MH. METHODS: The system integrates magnetomotive (MMUS) and thermal ultrasound imaging with MH. An ultrasound device was used to acquire MMUS images to detect MNPs, and ultrasound thermometry to monitor the temperature. This platform was designed such that a single coil generated the magnetic field for MMUS and MH. The feasibility of the system was examined using a tissue mimicking phantom containing an inclusion filled with zinc substituted magnetite NPs. RESULTS: These MNPs were effectively used as contrast agent for MMUS and to generate heat during MH. In addition to localizing MNPs, real-time two-dimensional temperature maps were obtained with substantial concordance (ρc > 0.97) with invasive measurements using fiber optic thermometer. The heating rate was proportional to the displacements in MMUS (r = 0.92). CONCLUSION: Ultrasound thermometry was successfully used to monitor the temperature during MH. In addition, it was shown that acquiring MMUS images prior to MH can qualitatively predict the temperature distribution of the MNP-laden regions.

Role of zinc substitution in magnetic hyperthermia properties of magnetite nanoparticles: interplay between intrinsic properties and dipolar interactions.

Optimizing the intrinsic properties of magnetic nanoparticles for magnetic hyperthermia is of considerable concern. In addition, the heating efficiency of the nanoparticles can be substantially influenced by dipolar interactions. Since adequate control of the intrinsic properties of magnetic nanoparticles is not straightforward, experimentally studying the complex interplay between these properties and dipolar interactions affecting the specific loss power can be challenging. Substituting zinc in magnetite structure is considered as an elegant approach to tune its properties. Here, we present experimental and numerical simulation results of magnetic hyperthermia studies using a series of zinc-substituted magnetite nanoparticles (ZnxFe1-xFe2O4, x = 0.0, 0.1, 0.2, 0.3 and 0.4). All experiments were conducted in linear regime and the results were inferred based on the numerical simulations conducted in the framework of the linear response theory. The results showed that depending on the nanoparticles intrinsic properties, interparticle interactions can have different effects on the specific loss power. When dipolar interactions were strong enough to affect the heating efficiency, the parameter σ = KeffV/kBT (Keff is the effective anisotropy and V the volume of the particles) determined the type of the effect. Finally, the sample x = 0.1 showed a superior performance with a relatively high intrinsic loss power 5.4 nHm2kg-1.

The effect of magnetization of natural rubber latex-coated magnetite nanoparticles on shear wave dispersion magneto-motive ultrasound.

The shear wave dispersion magneto-motive ultrasound (SDMMUS) method was recently developed to analyze the mechanical properties of a viscoelastic medium. This technique is based on the interaction of magnetic nanoparticles (MNPs) with an external magnetic field to generate a shear wave within the medium labeled with MNPs. The propagation of this wave provides information about the viscoelastic properties of the medium. In a previous work by Arsalani et al (2018), magnetite NPs were synthesized by a co-precipitation method and coated with natural rubber latex (NRL). In order to investigate the effect of NRL on the size and magnetization of MNPs, varying amounts of NRL (zero, 100 µl, and 800 µl of a stock solution of NRL) were used during the synthesis process. The results showed that MNPs prepared with 800 µl of NRL, named as MNPs-800NRL, had the smallest size and highest magnetization. In the present paper, the main objective is to investigate whether MNPs-800NRL, having the highest magnetization, is also the best option for SDMMUS experiments among others. All experiments were performed using gelatin tissue-mimicking phantoms labeled with the aforementioned MNPs. The two factors of core size and magnetization were considered, and based on the observed results, the effect of magnetization was more prominent than that of the core size on the induced displacements. MNPs coated with a thicker NRL shell, having the highest magnetization value, enhanced the sensitivity and the signal to noise ratio in SDMMUS. Various concentrations of these optimized MNPs were also examined, to investigate the lowest possible concentration for observing shear waves in the SDMMUS technique.

A versatile induction heating system for magnetic hyperthermia studies under different experimental conditions.

In recent decades, magnetic hyperthermia using magnetic nanoparticles, a promising but quite challenging method, has proven to be an effective cancer therapy procedure. In hyperthermia, heat, which is generated by magnetic nanoparticles exposed to a radiofrequency magnetic field, is employed to battle cancerous cells. Ideally, devices for magnetic hyperthermia should provide a variety of field amplitudes and frequencies for generating an appropriate and powerful alternating magnetic field. Here, we report the design and evaluation of a versatile system which provides different experimental setup possibilities for magnetic hyperthermia. The proposed system is a derivative of the Mazzilli inverter, which directly follows the resonant frequency of the LC tank circuit independent of its component. The feasibility of the system for hyperthermia studies was examined using iron oxide nanoparticles prepared by the coprecipitation method. Different experimental conditions including nanoparticles in solution and dispersed in gelatin phantoms were evaluated. Four different coils including two solenoids, a pancake, and a Helmholtz-like format were successfully tested. Using these coils, 18 different operation frequencies in the frequency band of 63-530 kHz with field strengths up to 27.2 kA/m were achieved.