Noninvasive Microwave Hyperthermia Research Articles

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.

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.

Non-Invasive Microwave Hyperthermia and Simultaneous Temperature Monitoring with a Single Theranostic Applicator.

Cancer therapies are constantly evolving. Currently, heating tumor tissue is becoming more accessible as a stand-alone method or in combination with other therapies. Due to its multiple advantages over other heating mechanisms, microwave hyperthermia has recently gained a lot of traction. In this work, we present a complementary split-ring resonator that is simultaneously excited in two independent frequency bands. With a high-power signal, the applicator is excited and heats the tissue-under-test up to 50°C with an average heating rate of 0.72°C per second. Furthermore, we present a dielectric temperature control system using the same applicator for microwave hyperthermia applications, which currently still requires an additional thermometry system. By exciting the applicator with a low-power signal, we can constantly monitor its resonant frequency. This resonant frequency depends on the tissue properties, which in turn are temperature-dependent. In the temperature range from 20-50°C, a positive correlation between the temperature and resonant frequency was established.Clinical relevance - Exploiting the dual-band behavior of the complementary split-ring resonator to heat the tissue-under-test while dielectrically monitoring its temperature, creates new possibilities towards a theranostic, non-invasive microwave hyperthermia applicator.

Non-invasive microwave hyperthermia for bone cancer treatment using realistic bone models and flexible antenna arrays

ABSTRACT In this manuscript, a method for noninvasive microwave hyperthermia treatment for bone cancer is proposed. In the proposed method, noninvasive microwave hyperthermia of cancer patient-specific bone models is practiced using an antenna array based on the beamforming technique to locally raise the temperature of the tumor to healing values during keeping healthy tissue at body temperature. The excitation properties of the antenna array elements have been optimized using the Trust Region Framework optimization technique in order to accurately focus. The proposed method is examined at 2.7 and 4.5 GHz, using a flexible antenna array of 1 × 4 antenna elements. Based on the hyperthermia simulation results, when the antenna excitation properties are determined by optimization, it is observed that positive results can be obtained for the treatment of tumorous tissue. In the proposed technique, it is achieved by keeping the heating effect at minimum values in healthy tissues and focusing the power in the tumor position by applying electromagnetic waves to the patient-specific bone model.

Efficient focusing of microwave hyperthermia for small deep-seated breast tumors treatment using particle swarm optimization

Focused microwave hyperthermia is a technique with advantage of high accuracy and low side effects for breast tumor treatments. In this study, an efficient focusing technique for noninvasive microwave hyperthermia treatment for breast tumors is presented. Particle Swarm Optimization (PSO) is used to find the optimum excitations (phases and amplitudes) of a three dimension (3D) Micro-Strip Patch (MSP) antenna array operating at 2.45 GHz. The antenna excitations are optimized to maximize the power loss density and the Specific Absorption Rate (SAR) at the tumor location, to reach the required hyperthermia temperature (above 42 °C) at the tumor location without causing hot spots in healthy tissues. The technique is tested on a challenging scenario of a 3D realistic breast model having a tumor less than 1 cm3 volume and embedded in different locations deep in the glandular tissue of a very dense breast. The results confirmed the capability of the focusing technique.

3-D Focused Microwave Hyperthermia for Breast Cancer Treatment With Experimental Validation

A 3-D focusing technique for noninvasive microwave hyperthermia treatment for breast cancer is presented and experimentally validated. The 3-D focusing is conducted to find the optimum excitations (phases and amplitudes) of a 3-D antenna array surrounding the breast using particle swarm optimization. The focusing approach aims at producing the required temperature (42 °C) at a tumor anywhere in the breast without causing hot spots in healthy tissue. Based on the modeling, a microwave system, which includes a 4.2-GHz source, power amplifier, two-stage power dividers, and phase shifters in addition to 24-element antenna array, was designed, built, and tested. The test was performed on the challenging scenario of a very dense breast phantom having 1-cm3 tumor embedded in glands. The experiments were conducted on a 3-D printed phantom that has realistic dielectric and thermal properties. The breast phantom was irradiated for one hour while the temperature distribution was recorded by thermal imager at different time intervals. The results confirmed the capability of the proposed 3-D focusing technique and experimental system in using 65-W microwave power to elevate the temperature at tumor to more than 42 °C while keeping healthy tissue safe at 36 °C without any hot spots.

Three-Dimensional Microwave Hyperthermia for Breast Cancer Treatment in a Realistic Environment Using Particle Swarm Optimization.

In this paper, a technique for noninvasive microwave hyperthermia treatment for breast cancer is presented. In the proposed technique, microwave hyperthermia of patient-specific breast models is implemented using a three-dimensional (3-D) antenna array based on differential beam-steering subarrays to locally raise the temperature of the tumor to therapeutic values while keeping healthy tissue at normal body temperature. This approach is realized by optimizing the excitations (phases and amplitudes) of the antenna elements using the global optimization method particle swarm optimization. The antennae excitation phases are optimized to maximize the power at the tumor, whereas the amplitudes are optimized to accomplish the required temperature at the tumor. During the optimization, the technique ensures that no hotspots exist in healthy tissue. To implement the technique, a combination of linked electromagnetic and thermal analyses using MATLAB and the full-wave electromagnetic simulator is conducted. The technique is tested at 4.2 GHz, which is a compromise between the required power penetration and focusing, in a realistic simulation environment, which is built using a 3-D antenna array of 4 × 6 unidirectional antenna elements. The presented results on very dense 3-D breast models, which have the realistic dielectric and thermal properties, validate the capability of the proposed technique in focusing power at the exact location and volume of tumor even in the challenging cases where tumors are embedded in glands. Moreover, the models indicate the capability of the technique in dealing with tumors at different on- and off-axis locations within the breast with high efficiency in using the microwave power.

Microwave Hyperthermia for Breast Cancer Treatment Using Electromagnetic and Thermal Focusing Tested on Realistic Breast Models and Antenna Arrays

A technique for noninvasive microwave hyperthermia treatment for breast cancer is presented. In the proposed technique, electromagnetic (EM) focusing on patient-specific breast models is implemented to concentrate the power at the tumor position while keeping the power levels at other positions (healthy tissues) at minimum values. This step is realized by optimizing phase excitations of the utilized antenna elements. In the next step, a thermal analysis is used to determine the scaling factor of the antennas’ excitation amplitudes to realize the required temperature at the tumor position. A closed-loop procedure ensures that there are no hot spots in any of the healthy tissues. The technique is tested in a realistic environment which includes three-dimensional breast models and antenna arrays. The presented results on fatty and dense breast models using two types of directional antennas validate the proposed technique. The investigations across wide frequency bands indicate that the frequencies around 4.2 and 4.5 GHz are optimum values for the hyperthermia treatment of dense and fatty breasts, respectively.

A COMPARISON BETWEEN DIFFERENT SCHEMES OF MICROWAVE CANCER HYPERTHERMIA TREATMENT BY MEANS OF LEFT-HANDED METAMATERIAL LENSES

In the hyperthermia therapy, multiple microwave sources can be arranged with appropriate spacing around the tissue containing tumor by using left-handed material (LHM) lenses. We employ some low loss LHM lenses schemes for an effective non-invasive microwave hyperthermia treatment of large tumors up to several centimeters of depth inside the biological tissues. Different configurations of LHM lenses are proposed and compared in order to assess the efficiency of hyperthermia treatment. High-resolution focusing of microwave radiation can be achieved by joint heating of several microwave antennas behind a conformal flat LHM lens. We show that a microwave radiation can be effectively focused in a 1.2 cm diameter tumor located within a lossy breast tissue. The results show that hyperthermia (temperature over 42 ◦ ) is reached and then maintained for one hour without involving the surrounding healthy tissues. Lastly, the heating area is adjusted in both lateral and longitudinal directions changing the position of the microwave sources or selecting LHM lenses with different thickness. This approach confirms that the conformal four-lens system is more efficient to achieve microwave tumor hyperthermia than single- and double-lens schemes.

Focusing time harmonic scalar fields in non-homogenous lossy media: Inverse filter vs. constrained power focusing optimization

Two strategies to focus time harmonic scalar fields in known inhomogeneous lossy media are compared. The first one is the Inverse Filter (IF) method, which faces the focusing task as the synthesis of a nominal field. The second one is the Constrained Power Focusing Optimization (CPFO) method, which tackles the problem in terms of constrained mask constrained power optimization. Numerical examples representative of focusing in noninvasive microwave hyperthermia are provided to show that CPFO is able to outperform IF, thanks to the additional degrees of freedom arising from the adopted power synthesis formulation.

3D computational study of non-invasive patient-specific microwave hyperthermia treatment of breast cancer

Non-invasive microwave hyperthermia treatment of breast cancer is investigated using three-dimensional (3D) numerical breast phantoms with anatomical and dielectric-properties realism. 3D electromagnetic and thermal finite-difference time-domain simulations are used to evaluate the focusing and selective heating efficacy in four numerical breast phantoms with different breast tissue densities. Beamforming is used to design and focus the signals transmitted by an antenna array into the breast. We investigate the use of propagation models of varying fidelity and complexity in the design of the transmitted signals. An ideal propagation model that is exactly matched to the actual patient's breast is used to establish a best-performance baseline. Simpler patient-specific propagation models based on a homogeneous breast interior are also explored to evaluate the robustness of beamforming in practical clinical settings in which an ideal propagation model is not available. We also investigate the performance of the beamformer as a function of operating frequency and compare single-frequency and multiple-frequency focusing strategies. Our study suggests that beamforming is a robust method of non-invasively focusing microwave energy at a tumor site in breasts of varying volume and breast tissue density.

Computational feasibility of deformable mirror microwave hyperthermia technique for localized breast tumors

Purpose: Computational feasibility of a new non-invasive microwave hyperthermia technique that employs dual deformable mirror is investigated using simplified computational tools and anatomically realistic breast models.Materials and methods: The proposed technique employs two pairs of electromagnetic sources and continuously deformable mirrors to focus the electromagnetic radiation at the target site for hyperthermia. The mirror functions like a continuum of radiating elements that offer effective scan coverage inside the breast with efficient field focusing at the target location. The electric field focusing and temperature mapping in the two-dimensional numerical simulations are investigated using wave propagation and bio-heat transfer models respectively. The method of moments, a popular numerical simulation tool, is used to model the electric field maintained by the deformable mirrors for continuous wave excitation. The electromagnetic (EM) energy deposited by the mirrors is used in the steady state bio-heat transfer equation to quantify the temperature distribution inside two-dimensional anatomically realistic breast models.Results: Feasibility of the proposed technique is evaluated using numerical breast models derived from magnetic resonance images of patients with variation in breast density, age and pathology.Conclusions: The computational study indicates preferential EM energy deposition and temperature elevation inside tumor tissue with minimum collateral damage to the neighboring normal tissues. Simulation results obtained for the magnetic resonance (MR) breast data appear promising and indicate the merit in pursuing the investigation using 3D computational models.

Enhancement of anticancer drug delivery to the brain by microwave induced hyperthermia

Methotrexate (MTX) is a widely prescribed antifolate in cancer chemotherapy for a variety of neoplasms. Like many useful, hydrophilic antitumor drugs, MTX is excluded from the brain after systemic administration due to its inability to cross the blood–brain barrier (BBB). The blood–brain barrier functions as a differential filter which permits the selective passage of substance from blood to extracellular brain spaces. It maintains the physical and chemical environments of the brain within certain narrow limits. We have studied enhanced uptake of MTX in brains of male rats (10-week old Wistar, 500 g, three per group) subjected to selective microwave hyperthermia of the left hemisphere. The rat was anesthetized using 40 mg/kg of sodium pentobarbital, IP and was placed in a stereotaxic head holder. Microwave energy (2450 MHz, 2.6 W/cm 2, 208 W/kg, CW) was applied for 20 min. The body temperature was kept at 37.8±0.4°C. The brain temperature recorded in a similar group of rats using a carbon filament probe (Vitek) was 42.7±0.4°C. Three different MTX dosages, 50, 100, and 200 mg/kg, were injected intravenously immediately following microwave irradiation into the rat in 1.5, 3 and 6 min, respectively. The drug was allowed to circulate for 5 min before brains were removed for analysis. Standard HPLC assays were applied to samples from the anterior and posterior left hemisphere of the cerebrum, and the cerebellum. Samples from the right hemisphere were used for controls. The average uptake at the posterior left hemisphere was found to be 2.25±0.43, 10.40±2.59, and 17.23±1.13 μg of MTX per g of brain tissue for 50, 100, and 200 mg/kg doses, respectively. In another series of experiments, MTX bolus was not injected until 15 or 45 min after cessation of microwave irradiation. Brains of rats injected 45 min after irradiation were free of MTX. Animals euthanized 15 min post-irradiation had an average midbrain MTX concentration of 2.5±0.46 μg/g of tissue. These results indicate that MTX uptake is significantly increased in rat brains subjected to noninvasive microwave hyperthermia treatment. Furthermore, the increase is reversible within 45 min post-irradiation.

FDTD verification of deep-set brain tumor hyperthermia using a spherical microwave source distribution

Although use of noninvasive microwave hyperthermia to treat cancer is problematic in many human body structures, careful selection of the source electric field distribution around the entire surface of the head can generate a tightly focused global power density maximum at the deepest point within the brain. An analytic prediction of the optimum volume field distribution in a layered concentric head model based on summing spherical harmonic modes is derived and presented. This ideal distribution is then verified using a three-dimensional finite difference time domain (FDTD) simulation with a discretized, MRI-based head model excited by the spherical source. The numerical computation gives a very similar dissipated power pattern as the analytic prediction. This study demonstrates that microwave hyperthermia can theoretically be a feasible cancer treatment modality for tumors in the head, providing a well-resolved "hot-spot" at depth without overheating any other healthy tissue.

Graded Spinal Cord Injuries Produced in Rabbits with Non-Invasive Microwave Hyperthermia

The use of non-invasive microwave energy to produce spinal cord injuries with intraspinal hyperthermia was studied in experimental animals. Lesions were produced with external beam microwave irradiation at 915 MHz in rabbits, using intraspinal temperature levels from 40 to 43 degrees C., and periods of heating ranging from 15 to 60 minutes. The parameters which determined thermal dose were the degree of temperature elevation in the spinal cord relative to the body core and the duration of that elevation. Thermal dose-response relationships were established by monitoring intraspinal temperatures during heating using an epidural thermistor probe at T8. Animals were examined 48 hours after lesion production and assigned a neurological grade. Injuries were grouped clinically according to their degree of relative functional severity as minimal, mild, moderate, or severe. Evaluation of spinal cord integrity was carried out by recording cortical somatosensory evoked responses (SER) following sciatic nerve stimulation. Increased SER latencies were first observed after heating the spinal cord to 41 degrees for 60 minutes. Impulse transmission was absent after heating to 42 degrees for 30 minutes, a thermal dose which produced complete paraplegia. Morphologically, lesion size and configuration were directly related to the thermal dose used in their production. Low thermal doses produced white matter edema limited to the posterior columns, while larger doses resulted in demyelination, retrograde neuronal changes, and infarction of the dorsal half of the cord. High thermal doses also produced foci of hemorrhage in the gray and white matter of the dorsal cord. These studies suggest that reproducible spinal cord injuries with predictable levels of neurological severity can be produced by noninvasive microwave heating.(ABSTRACT TRUNCATED AT 250 WORDS)

Localized Hyperthermia with Electromagnetic Arrays and the Leaky-Wave Troughguide Applicator

Noninvasive microwave hyperthermia is an attractive cancer treatment modality. Understanding the advantages and limitations of focusing are vital for the practical implementations of electromagnetic heating of deep tumors. These, as well as the important issues of tissue coupling and proper choices of polarization and frequency are herein examined. An optimal theoretical source distribution and an applicator design that approximates this distribution are discussed.