Microwave Hyperthermia Research Articles

Structure, magnetic, and electrodynamic properties of SrInxFe12‐xO4/Ni0.5Zn0.5Fe2O4 composites at low temperature

AbstractExchange‐coupled hard–soft bi‐magnetic ferrites can be used as isolators, microwave absorption materials, filters, hyperthermia materials, and biosensors with improved energy properties. The nanocomposites with the chemical composition SrInxFe12‐xO4/Ni0.5Zn05Fe2O4 (where x varies from 0.00 to 0.04) have the advantages of both materials: spinel and hexaferrite. The combination of Sr‐hexaferrate with spinel ferrite results in proximity effects, reversal of magnetization in two stages, and blocking temperatures that can be tuned in bi‐magnetic hard and soft ferrites. It was found an anomalius kink in the hysteresis loops and two peaks in the switching field distribution at x ≤ 0.02. The exchange interaction on the surfaces of hard and soft nanoparticles explains the behavior of the magnetic characteristics.

Optimization of Antenna Excitations for Non-Invasive Microwave Hyperthermia for Breast Cancer Treatment

This research demonstrates an effective focused microwave hyperthermia for non-invasive breast cancer treatment at early stages where the tumour size is small and has not spread to nearby tissues. First, a three-dimensional (3-D) Micro-Strip Patch (MSP) antenna array consisting of four elements and operating at 2.45GHz is used. Second, two evolutionary optimization techniques, particle swarm optimization (PSO) and genetic algorithm (GA), are compared in terms of optimization speed in order to select the algorithm which will be used in this study to calculate the ideal phase and amplitude excitations for each MSPA. The fitness function of the used algorithm aims to increase the specific absorption rate (SAR) and power density (Q) at the tumour site while keeping these values at minimum levels in healthy positions. The focusing technique is used to collect a data of accurate antenna excitations of a tumour having a radius of 2.5 mm (less than 1 cm3 volume), embedded in every possible position in the glandular tissues in the antenna array's central plane. Using MRI results from a real patient (age 40) in the prone position, a realistic breast model was produced. In order to demonstrate the efficiency of the suggested 3D microwave focusing technology, the temperature distribution at the tumour centre position was measured and compared with other healthy locations. The data gathered are then used to create a non-invasive hyperthermia GUI system for the treatment of breast cancer.

Application of an artificial intelligence segmentation for deep hyperthermia treatment planning in the pelvic region

During a microwave hyperthermia oncology treatment, the target region temperature is elevated to the temperatures of 40–44 °C, which improves the therapeutic effect of a standard radiotherapy and/or chemotherapy treatments. Amplitudes and phases of antenna input signals in the phased array setup surrounding the 3D patient model are optimised with respect to maximise the energy deposition in the target region. In this study, we successfully integrated an automatic artificial intelligence segmentation routine, used for patient-specific 3D model generation, into the hyperthermia treatment planning process. This allows us to apply more realistic patient 3D model for the online hyperthermia guidance including detailed retrospective analyses of the overall treatment quality, possibly leading to a widespread clinical use of the hyperthermia treatment planning.

Application of Hyperthermia for Cancer Treatment: Various Techniques and Recent Advancement

Cancer is a disease characterized by uncontrollable cell division in a specific area of the body. It is a leading cause of death, and its prevalence is increasing. There are numerous techniques and protocols employed, including as chemotherapy, radiography, surgical tumor removal, etc. However, these procedures have a number of negative side effects that cause excruciating pain and intense anxiety in the patients. It has been increasingly difficult to find new cancer-fighting strategies during the past few decades. One of the best cancer treatment choices is hyperthermia, an ancient form of therapy that offers fresh hope when paired with engineering methods. This study examines the crucial data for the coupling with hyperthermia of various engineering techniques, which is carefully organized according to the techniques used, such as hyperthermic perfusion, frequency enhancers, ultrasonic hyperthermia, external radio-frequency devices, microwave hyperthermia, using a catheter, heat the target area before injecting superparamagnetic and magnetic nanoparticles.

A two-stage exacerbated hypoxia nanoengineering strategy induced amplifying activation of tirapazamine for microwave hyperthermia-chemotherapy of breast cancer

Microwave hyperthermia (MH) is an emerging treatment for solid tumors, such as breast cancer, due to its advantages of minimally invasive and deep tissue penetration. However, MH induced tumor hypoxia is still an obstacle to breast tumor treatment failure. Therefore, an original nanoengineering strategy was proposed to exacerbate hypoxia in two stages, thereby amplifying the efficiency of activating tirapazamine (TPZ). And a novel microwave-sensitized nanomaterial (GdEuMOF@TPZ, GEMT) is designed. GdEuMOF (GEM) nanoparticles are certified excellent microwave (MW) sensitization performance, thus improving tumor selectivity to achieve MH. Meanwhile MW can aggravate the generation of thrombus and caused local circulatory disturbance of tumor, resulting in the Stage I exacerbated hypoxia environment passively. Due to tumor heterogeneity and uneven hypoxia, GEMT nanoparticles under microwave could actively deplete residual oxygen through the chemical reaction, exacerbating hypoxia level more evenly, thus forming the Stage II of exacerbated hypoxia environment. Consequently, a two-stage exacerbated hypoxia GEMT nanoparticles realize amplifying activation of TPZ, significantly enhance the efficacy of microwave hyperthermia and chemotherapy, and effectively inhibit breast cancer. This research provides insights into the development of progressive nanoengineering strategies for effective breast tumor therapy.

Microwave-responsive gadolinium metal-organic frameworks nanosystem for MRI-guided cancer thermotherapy and synergistic immunotherapy

The clinical application of cancer immunotherapy is unsatisfied due to low response rates and systemic immune-related adverse events. Microwave hyperthermia can be used as a synergistic immunotherapy to amplify the antitumor effect. Herein, we designed a Gd-based metal-organic framework (Gd-MOF) nanosystem for MRI-guided thermotherapy and synergistic immunotherapy, which featured high performance in drug loading and tumor tissue penetration. The PD-1 inhibitor (aPD-1) was initially loaded in the porous Gd-MOF (Gd/M) nanosystem. Then, the phase change material (PCM) and the cancer cell membrane were further sequentially modified on the surface of Gd/MP to obtain Gd-MOF@aPD-1@CM (Gd/MPC). When entering the tumor microenvironment (TME), Gd/MPC induces immunogenic death of tumor cells through microwave thermal responsiveness, improves tumor suppressive immune microenvironment and further enhances anti-tumor ability of T cells by releasing aPD-1. Meanwhile, Gd/MPC can be used for contrast-enhanced MRI. Transcriptomics data revealed that the downregulation of MSK2 in cancer cells leads to the downregulation of c-fos and c-jun, and ultimately leads to the apoptosis of cancer cells after treatment. In general, Gd/MPC nanosystem not only solves the problem of system side effect, but also achieves the controlled drug release via PCM, providing a promising theranostic nanoplatform for development of cancer combination immunotherapy.

Numerical evaluation of heat-triggered drug release via thermo-sensitive liposomes: A comparison between image-based vascularized tumor and volume-averaged porous media models

In this study, two numerical models for controlled drug delivery through thermo-sensitive liposomes under mild microwave hyperthermia are compared. The first model simulates blood flow directly in a realistic tumor vascular network. The second one, at the volume-averaged macro scale, employs the porous media model. Using the vascular-scale approach is helpful for these kind of applications since the porous media assumption does not allow to account for local vascular blood flow, which is a crucial variable to quantify outputs like local drug accumulations. In the present study, the vascularized tumor model is obtained from a photo-acoustic scan and used as computational domain. The vascular-scale model considers heat and drug transfer in vascular and intracellular spaces, employing energy equations for heat transfer and a three-compartment convection-diffusion model for drug diffusion. Blood flow is simulated using the momentum equation for non-Newtonian fluids. The volume-averaged model shows good agreement with the vascular-scale model even if provides less precise information about temperature field distribution and drug localization within the tumor tissue. Also, the volume-averaged model underestimates Fraction of Killed Cells by 3 % post-treatment, presenting a more uniform temperature field and drug distribution compared to the vascular-scale one. Despite these small limitations, the porous media model is reliable for obtaining average results, while the vascular-scale model is suitable when more accurate results are needed. This study's findings aid those who aim to predict hyperthermia-driven drug delivery, suggesting the vascular-scale approach for precision and accuracy and the volume-averaged approach for average outcomes.

Thermally boosted interstitial high-dose-rate brachytherapy in high-risk early-stage breast cancer conserving therapy - large cohort long-term results.

Early-stage high-risk breast cancer (BC) is standardly treated with breast-conserving therapy (BCT), combined with systemic therapy and radiotherapy (RT) ± tumor bed boost, e.g., with interstitial high-dose-rate brachytherapy (HDR-BT). To improve local recurrence rate (LRR), BT radiosensitization (thermal boost, TB) with interstitial microwave hyperthermia (MWHT) may be an option. The paper aims to report a retrospective single-institutional study on 5- and 10-year local control (LC), distant metastasis-free survival (DMFS), disease-free survival (DFS), overall survival (OS), cosmetic outcome (CO), and late toxicity (fibrosis, fat necrosis) after thermally enhanced HDR-BT boost to the BC tumor bed. In 2006-2018, 557 early-stage (I-IIIA) high-risk BC patients were treated with BCT. If indicated, they were administered systemic therapy, then referred for 40.0-50.0 Gy whole breast irradiation (WBI) and 10 Gy interstitial HDR-BT boost (group A). Eligible patients had a single MWHT session preceding BT (group B). Based on present risk factors (RF), medium-risk (1-2 RF) and high-risk subgroups (≥ 3 RF) were formed. Patients were standardly checked, and control mammography (MMG) was performed yearly. Breast cosmesis (Harvard scale) and fibrosis were recorded. LC, DMFS, DFS, and OS were statistically analyzed. Out of 557 patients aged 57 years (26-84), 364 (63.4%) had interstitial HDR-BT boost (group A), and 193 (34.6%) were preheated with MWHT (group B). Patients in group B had a higher clinical stage and had more RFs. The median follow-up was 65.9. Estimated 5-year and 10-year LC resulted in 98.5% and 97.5%, respectively. There was no difference in LC, DMFS, DFS, and OS between groups A and B and between extracted high-risk subgroups A and B. Five- and ten-year OS probability was 95.4% and 88.0%, respectively, with no difference between groups A and B. Harvard criteria-based CO assessment revealed good/excellent cosmesis in 74.9-79.1%. Tumor bed hardening was present in 40.1-42.2%. Asymptomatic fat necrosis-related macrocalcifications were detected in 15.6%, more frequently in group B (p = 0.016). Thermally boosted or not, HDR-BT was locally highly effective as part of combined treatment. Five- and ten-year LC, DMFS, DFS, and OS were high and equally distributed between the groups, although TB was prescribed in more advanced one with more RFs. TB did not influence CO and fibrosis. TB added to late toxicity regarding asymptomatic fat necrosis detected on MMG.

Metamaterial based AMC backed archimedean spiral antenna for in-vitro microwave hyperthermia of skin cancer

ABSTRACT This research article presents a study that uses microwave frequencies (ISM band) for treatment of skin cancer by heating the malignant cells on skin with a Microwave Hyperthermia (MWHT) applicator. The proposed MWHT applicator has been designed as an Archimedean Spiral Microstrip Patch Antenna (AMSPA) of dimensions 38 × 38 × 1.64 mm3 backed with a Meshed-shaped AMC (48 × 48 × 3.27mm3) reflector, placed at an optimized distance of 12 mm from AMSPA. The proposed AMSPA is designed as a single spiral resonator and fabricated on FR-4 substrate, excited using a feed network. The proposed AMSPA shows a resonance at 2.5 GHz with an impedance BW of 260 MHz (2.37–2.63 GHz) and peak gain of 3.20 dB with a bidirectional radiation pattern. An AMC is placed at its backside that can be exploited as a phase-compensation surface to attain an in-phase profile for directive emission and improve the BW upto 470 MHz, peak gain to 6.8 dB and also enhance the front-to-back ratio of the radiating antenna with radiation efficiency of 80%. The simulated environment for hyperthermia analysis is set up using penne’s Bio-Heat equations to deliver microwave energy to the bio-mimic, that leads to a rise in temperature over the designed bio-mimic in CST MWS in the range of 41–45°C. The validation of MWHT radiation properties and temperature rise inside the malignancy of phantom is carried out by fabricating the bio-mimic using gelatine, vegetable oils and glycerol. This set up enhances the penetration-depth of EM waves inside the tri-layered phantom up-to 29.5 mm with Effective Field Surface of 36 × 36 mm2 and SAR of 8 W/Kg.

An Ultra-small Heated Area Masked Microwave Hyperthermia Therapy Scheme in Fresnel Region

This paper introduces a localized masked thermal therapy method for only the breast through the Fresnel region. A pyramidal horn antenna has been used as a hyperthermia system applicator. The antenna is fed by a Yagi array and resonates at 4.74 GHz. A metal plate with a square slot masked the breast phantom. The antenna irradiates the breast phantom for 5 and 10 minutes with input power of 10 and 20 watts (W). Thermal and specific absorption rate (SAR) distributions are studied under the same conditions for a fair comparison between masked and unmasked system performance. The square slot dimensions are altered, and their effects are studied considering the phantom heated area. Moving from unmasked to masked hyperthermia scenarios, a heated area size reduction of 99.87 % is achieved along with a very considerable SAR value reduction. The masked scenario elevates the breast temperature to 43 C∘ in a very concentrated area. The proposed system can elevate only an area of 2×2mm2 of the breast tissue to a temperature of 40 C∘ in 5 minutes, and that is a very promising result in hyperthermia therapy applications.

Comparison of Microwave Hyperthermia Applicator Designs with Fora Dipole and Connected Array.

In microwave hyperthermia tumor therapy, electromagnetic waves focus energy on the tumor to elevate the temperature above its normal levels with minimal injury to the surrounding healthy tissue. Microwave hyperthermia applicator design is important for the effectiveness of the therapy and the feasibility of real-time application. In this study, the potential of using fractal octagonal ring antenna elements as a dipole antenna array and as a connected array at 2.45 GHz for breast tumor hyperthermia application was investigated. Microwave hyperthermia treatment models consisting of different fractal octagonal ring antenna array designs and a breast phantom are simulated in COMSOL Multiphysics to obtain the field distributions. The antenna excitation phases and magnitudes are optimized using the global particle swarm algorithm to selectively increase the specific absorption rate at the target region while minimizing hot spots in other regions within the breast. Specific absorption rate distributions, obtained inside the phantom, are analyzed for each proposed microwave hyperthermia applicator design. The dipole fractal octagonal ring antenna arrays are comparatively assessed for three different designs: circular, linear, and Cross-array. The 16-antenna dipole array performance was superior for all three 1-layer applicator designs, and no distinct difference was found between 16-antenna circular, linear, or cross arrays. Two-layer dipole arrays have better performance in the deep-tissue targets than one-layer arrays. The performance of the connected array with a higher number of layers exceeds the performance of the dipole arrays in the superficial regions, while they are comparable for deep regions of the breast. The 1-layer 12-antenna circular FORA dipole array feasibility as a microwave hyperthermia applicator was experimentally shown.

Multifunctional 3D-printed scaffolds eradiate orthotopic osteosarcoma and promote osteogenesis via microwave thermo-chemotherapy combined with immunotherapy

Tumor recurrence and a lack of bone-tissue integration are two critical concerns in the surgical treatment of osteosarcoma. Thus, an advanced multifunctional therapeutic platform capable of simultaneously eliminating residual tumor cells and promoting bone regeneration is urgently needed for efficient osteosarcoma treatment. Herein, to thoroughly eliminate tumors and simultaneously promote bone regeneration, an intelligent multifunctional therapeutic scaffold has been engineered by integrating microwave-responsive zeolitic imidazolate framework 8 (ZIF-8) nanomaterials loaded with a chemotherapeutic drug and an immune checkpoint inhibitor onto 3D-printed titanium scaffolds. The constructed scaffold features distinct microwave-thermal sensitization and tumor microenvironment-responsive characteristics, which can induce tumor immunogenic death by microwave hyperthermia and chemotherapy. Orthotopic implantation of the nanocomposite scaffold results in an enhanced immune response against osteosarcoma that may effectively inhibit tumor recurrence through synergistic immunotherapy. During long-term implantation, the zinc ions released from the degradation of ZIF-8 can induce the osteogenic differentiation of stem cells. The porous structure and mechanical properties of the 3D-printed titanium scaffolds provide a structural microenvironment for bone regeneration. This study provides a paradigm for the design of multifunctional microwave-responsive composite scaffolds for use as a therapy for osteosarcoma, which could lead to improved strategies for the treatment of the disease.

Flexible Graphene Sheet Loaded Curved Patch Applicator for Superficial Hyperthermia Treatment Planning Utilizing Ripple Effect of Armchair and Zigzag Bending

Background: Non-invasive microwave hyperthermia approaches suffer from several limitations, such as maximum energy localization in the target tissue, reduced unwanted hotspots, less penetration time at specific penetration depth, and maximum directivity of applicators. For conformal body structures, curved patch applicators avoid mismatch losses and provide circular polarization to achieve maximum power deposition at the target tissue. At microwave frequencies, graphene also exhibits good absorption properties and utilizing graphene strips on both sides of a curved patch offers potential benefits of enhancement of gain, directional radiation pattern, and suppressed sidelobes. Objective: Designing a flexible graphene sheet-loaded curved patch for a non-invasive microwave hyperthermia applicator resonating at 2.45 GHz is the prime objective of current work. The proposed work is based on utilizing the absorbing properties of graphene sheets with hybrid hexagonal boron nitride (hBN) under various bending conditions on both sides of a curved patch. Methods: Graphene-loaded curved design offers structural flexibility due to the presence of ripples on the surface and their alignment in armchair configuration (ARC) and zigzag configuration (ZGC). The bending flexibility along the two configurations alters the electronic properties and opens the band gap. Thus, the FEM model has been developed for coupling bio-electromagnetic problems of human body phantom with graphene-loaded curved patch applicator by bending it in two different configurations. Results: For both ARC and ZGC antenna design, parameters, such as return loss and realized gain, have been investigated. The proposed design achieved a maximum return loss value of -30 dB and gain of 7.1 dBi for ARC configuration since it provides the maximum difference in valance band and conduction band in band gap structure, while these values are relatively less in the case of ZGC. The implementation of the design on cylindrical body phantom is realized for ARC with a maximum Efield value of 80.2 V/m at a maximum penetration depth of 40 mm. Further simulations are performed for evaluation of penetration time and fractional tissue damage due to necrosis, and it has been observed that 10 W of input power is sufficient to achieve maximum temperature range and tissue necrosis in a duration of 15 minutes. Conclusion: The results show that a curved graphene patch applicator provides a potential solution for targeted heating in hyperthermia applications.

Thermal effects of electromagnetic origin from heating processes to biological disturbances due to field exposure—A review

This contribution aims to appraise, analyze and evaluate the literature relating to the interaction of electromagnetic fields (EMF) with matter and the resulting thermal effects. This relates to the wanted thermal effects via the application of fields as well as those uninvited resulting from exposure to the field. In the paper, the most popular EMF heating technologies are analyzed. This involves on the one hand high frequency induction heating (HFIH) and on the other hand microwave heating (MWH), including microwave ovens and hyperthermia medical treatment. Then, the problem of EMF exposure is examined and the resulting biological thermal effects are illuminated. Thus, the two most common cases of wireless EMF devices, namely digital communication tools and inductive power transfer appliances are analyzed and evaluated. The last part of the paper concerns the determination of the different thermal effects, which are studied and discussed, by considering the governing EMF and heat transfer (or bio heat) equations and their solution methodologies.

Microwave hyperthermia represses human papillomavirus oncoprotein activity and induces cell death due to cell stress in 3D tissue models of anogenital precancers and cancers

Hyperthermia is a well-accepted cancer therapy. Microwaves provide a very precise, targeted means of hyperthermia and are currently used to treat plantar warts caused by cutaneous-infective human papillomaviruses (HPVs). Other HPV genotypes infecting the anogenital mucosa cause genital warts or preneoplastic lesions or cervical cancer. Effective, non-ablative therapies for these morbid HPV-associated lesions are lacking. The molecular consequences of microwave treatment were investigated in invitro cultured three-dimensional HPV-positive cervical tumour tissues, and tissues formed from HPV-infected normal immortalised keratinocytes. Microwave energy delivery to tissues was quantified. Quantitative reverse transcriptase PCR was used to quantify mRNA expression. Immunohistochemistry and fluorescence immunostaining was used to assess protein expression. Microwave energy deposition induced sustained, localised cell death at the treatment site. There was a downregulation in levels of HPV oncoproteins E6 and E7 alongside a reduction in cellular growth/proliferation and induction of apoptosis/autophagy. HSP70 expression confirmed hyperthermia, concomitant with induction of translational stress. The data suggest that microwave treatment inhibits tumour cell proliferation and allows the natural apoptosis of HPV-infected cells to resume. Precision microwave delivery presents a potential new treatment for treating HPV-positive anogenital precancerous lesions and cancers. Funding was through an Innovate UK Biomedical Catalyst grant (ID# 92138-556187), a Chief Scientist Office grant (TCS/19/11) and core support from Medical Research Council (MC_ UU_12014) core funding for the MRC-University of Glasgow Centre for Virus Research.

Differential Evolution Optimization of Microwave Focused Hyperthermia Phased Array Excitation for Targeted Breast Cancer Heating.

Microwave hyperthermia using the phased array applicator is a non-invasive treatment modality for breast cancer. Hyperthermia treatment planning (HTP) is critical to accurately treating breast cancer and avoiding damage to the patient's healthy tissue. A global optimization algorithm, differential evolution (DE) algorithm, has been applied to optimize HTP for breast cancer and its ability to improve the treatment effect was proved by electromagnetic (EM) and thermal simulation results. DE algorithm is compared to time reversal (TR) technology, particle swarm optimization (PSO) algorithm, and genetic algorithm (GA) in HTP for breast cancer in terms of convergence rate and treatment results, such as treatment indicators and temperature parameters. The current approaches in breast cancer microwave hyperthermia still have the problem of hotspots in healthy tissue. DE enhances focused microwave energy absorption into the tumor and reduces the relative energy of healthy tissue during hyperthermia treatment. By comparing the treatment results of each objective function used in DE, the DE algorithm with hotspot to target quotient (HTQ) as the objective function has outstanding performance in HTP for breast cancer, which can increase the focused microwave energy of the tumor and decrease the damage to healthy tissue.

Temperature Monitoring During Microwave Hyperthermia Based on BP-Nakagami Distribution.

The purpose of this study is to accurately monitor temperature during microwave hyperthermia. We propose a temperature estimation model BP-Nakagami based on neural network for Nakagami distribution. In this work, we designed the microwave hyperthermia experiment of fresh ex vivo pork tissue and phantom, collected ultrasonic backscatter data at different temperatures, modeled these data using Nakagami distribution, and calculated Nakagami distribution parameter m. A neural network model was built to train the relationship between Nakagami distribution parameter m and temperature, and a BP-Nakagami temperature model with good fitting was obtained. The temperature model is used to draw the two-dimensional temperature distribution map of biological tissues in microwave hyperthermia. Finally, the temperature estimated by the model is compared with the temperature measured by thermocouples. The error between the temperature estimated by the temperature model and the temperature measured by the thermocouple is within 1°C in the range of 25°C-50°C for ex vivo pork tissue, and the error between the temperature estimated by the temperature model and the temperature measured by the thermocouple is within 0.5°C in the range of 25°C-50°C for phantom. The results show that the temperature estimation model proposed by us is an effective model for monitoring the internal temperature change of biological tissues.

Field and Temperature Shaping for Microwave Hyperthermia: Recent Treatment Planning Tools to Enhance SAR-Based Procedures.

The aim of the article is to provide a summary of the work carried out in the framework of a research project funded by the Italian Ministry of Research. The main goal of the activity was to introduce multiple tools for reliable, affordable, and high-performance microwave hyperthermia for cancer therapy. The proposed methodologies and approaches target microwave diagnostics, accurate in vivo electromagnetic parameters estimation, and improvement in treatment planning using a single device. This article provides an overview of the proposed and tested techniques and shows their complementarity and interconnection. To highlight the approach, we also present a novel combination of specific absorption rate optimization via convex programming with a temperature-based refinement method implemented to mitigate the effect of thermal boundary conditions on the final temperature map. To this purpose, numerical tests were carried out for both simple and anatomically detailed 3D scenarios for the head and neck region. These preliminary results show the potential of the combined technique and improvements in the temperature coverage of the tumor target with respect to the case wherein no refinement is adopted.

Antenna Arrangement in UWB Helmet Brain Applicators for Deep Microwave Hyperthermia.

Deep microwave hyperthermia applicators are typically designed as narrow-band conformal antenna arrays with equally spaced elements, arranged in one or more rings. This solution, while adequate for most body regions, might be sub-optimal for brain treatments. The introduction of ultra-wide-band semi-spherical applicators, with elements arranged around the head and not necessarily aligned, has the potential to enhance the selective thermal dose delivery in this challenging anatomical region. However, the additional degrees of freedom in this design make the problem non-trivial. We address this by treating the antenna arrangement as a global SAR-based optimization process aiming at maximizing target coverage and hot-spot suppression in a given patient. To enable the quick evaluation of a certain arrangement, we propose a novel E-field interpolation technique which calculates the field generated by an antenna at any location around the scalp from a limited number of initial simulations. We evaluate the approximation error against full array simulations. We demonstrate the design technique in the optimization of a helmet applicator for the treatment of a medulloblastoma in a paediatric patient. The optimized applicator achieves 0.3 °C higher T90 than a conventional ring applicator with the same number of elements.

PLGA Nanoparticles Loaded with Sorafenib Combined with Thermosensitive Hydrogel System and Microwave Hyperthermia for Multiple Sensitized Radiotherapy

Hypoxia is typically the leading cause of radiotherapy (RT) resistance in solid tumors, and glutathione (GSH) overexpression in tumor cells is a potent antioxidant mechanism that protects tumor cells from radiation damage. Herein, we developed a sorafenib (SFN) loaded-PLGA hydrogel system (SPH) in combination with microwave (MW) hyperthermia for RT sensitization. SPH with stable properties was produced by combining SFN and PLGA in a specific ratio and encapsulating the mixture in agarose hydrogel. Intratumoral injection of SPH to mice combined with MW hyperthermia can not only directly cause thermal damage to tumor cells, but also increase blood oxygen delivery to the tumor site, thus overcoming the problem of intratumoral hypoxia and achieving "first layer" RT sensitization. Moreover, high temperatures can cause the hydrogel to disintegrate and release SFN. Not only can SFN inhibit tumor growth, but it can also achieve the "second layer" of RT sensitization by inhibiting glutathione (GSH) synthesis in cells and increasing reactive oxygen species (ROS) production. Experiments, both in vitro and in vivo, have indicated that SPH and MW hyperthermia can achieve a double RT sensitization effect and a significant tumor inhibition effect. In conclusion, combining our SPH nanosystem and thermoradiotherapy is a promising anti-tumor treatment.