In Silico Study on Tumor-Size-Dependent Thermal Profiles inside an Anthropomorphic Female Breast Phantom Subjected to Multi-Dipole Antenna Array.
ABSTRACT: Electromagnetic hyperthermia as a potent adjuvant for conventional cancer therapies can be considered valuable in modern oncology, as its task is to thermally destroy cancer cells exposed to high-frequency electromagnetic fields. Hyperthermia treatment planning based on computer in silico simulations has the potential to improve the localized heating of breast tissues through the use of the phased-array dipole applicators. Herein, we intended to improve our understanding of temperature estimation in an anatomically accurate female breast phantom embedded with a tumor, particularly when it is exposed to an eight-element dipole antenna matrix surrounding the breast tissues. The Maxwell equations coupled with the modified Pennes' bioheat equation was solved in the modelled breast tissues using the finite-difference time-domain (FDTD) engine. The microwave (MW) applicators around the object were modelled with shortened half-wavelength dipole antennas operating at the same 1 GHz frequency, but with different input power and phases for the dipole sources. The total input power of an eight-dipole antenna matrix was set at 8 W so that the temperature in the breast tumor did not exceed 42 °C. Finding the optimal setting for each dipole antenna from the matrix was our primary objective. Such a procedure should form the basis of any successful hyperthermia treatment planning. We applied the algorithm of multi for multi-objective optimization for the power and phases for the dipole sources in terms of maximizing the specific absorption rate (SAR) parameter inside the breast tumor while minimizing this parameter in the healthy tissues. Electro-thermal simulations were performed for tumors of different radii to confirm the reliable operation of the given optimization procedure. In the next step, thermal profiles for tumors of various sizes were calculated for the optimal parameters of dipole sources. The computed results showed that larger tumors heated better than smaller tumors; however, the procedure worked well regardless of the tumor size. This verifies the effectiveness of the applied optimization method, regardless of the various stages of breast tumor development.
Project description:PURPOSE:To improve imaging performance for body MRI with a local transmit array at 10.5T, the geometry of a dipole antenna was optimized to achieve lower peak specific absorption rate (SAR) levels and a more uniform transmit profile. METHODS:Electromagnetic simulations on a phantom were used to evaluate the SAR and B1+ -performance of different dipole antenna geometries. The best performing antenna (the snake antenna) was simulated on human models in a 12-channel array configuration for safety assessment and for comparison to a previous antenna design. This 12-channel array was constructed after which electromagnetic simulations were validated by B1+ -maps and temperature measurements. After obtaining approval by the Food and Drug Administration to scan with the snake antenna array, in vivo imaging was performed on 2 volunteers. RESULTS:Simulation results on a phantom indicate a lower SAR and a higher transmit efficiency for the snake antenna compared to the fractionated dipole array. Similar results are found on a human body model: when comparing the trade-off between uniformity and peak SAR, the snake antenna performs better for all imaging targets. Simulations and measurements are in good agreement. Preliminary imaging result were acquired in 2 volunteers with the 12-channel snake antenna array. CONCLUSION:By optimizing the geometry of a dipole antenna, peak SAR levels were lowered while achieving a more uniform transmit field as demonstrated in simulations on a phantom and a human body model. The array was constructed, validated, and successfully used to image 2 individuals at 10.5T.
Project description:Microwave breast imaging has been reported as having the most potential to become an alternative or additional tool to the existing X-ray mammography technique for detecting breast tumors. Microwave antenna sensor performance plays a significant role in microwave imaging system applications because the image quality is mostly affected by the microwave antenna sensor array properties like the number of antenna sensors in the array and the size of the antenna sensors. In this paper, a new system for successful early detection of a breast tumor using a balanced slotted antipodal Vivaldi Antenna (BSAVA) sensor is presented. The designed antenna sensor has an overall dimension of 0.401? × 0.401? × 0.016? at the first resonant frequency and operates between 3.01 to 11 GHz under 10 dB. The radiating fins are modified by etching three slots on both fins which increases the operating bandwidth, directionality of radiation pattern, gain and efficiency. The antenna sensor performance of both the frequency domain and time domain scenarios and high-fidelity factor with NFD is also investigated. The antenna sensor can send and receive short electromagnetic pulses in the near field with low loss, little distortion and highly directionality. A realistic homogenous breast phantom is fabricated, and a breast phantom measurement system is developed where a two antennas sensor is placed on the breast model rotated by a mechanical scanner. The tumor response was investigated by analyzing the backscattering signals and successful image construction proves that the proposed microwave antenna sensor can be a suitable candidate for a high-resolution microwave breast imaging system.
Project description:A clinical treatment delivery platform has been developed and is being evaluated in a clinical pilot study for providing 3D controlled hyperthermia with catheter-based ultrasound applicators in conjunction with high dose rate (HDR) brachytherapy. Catheter-based ultrasound applicators are capable of 3D spatial control of heating in both angle and length of the devices, with enhanced radial penetration of heating compared to other hyperthermia technologies. Interstitial and endocavity ultrasound devices have been developed specifically for applying hyperthermia within HDR brachytherapy implants during radiation therapy in the treatment of cervix and prostate. A pilot study of the combination of catheter based ultrasound with HDR brachytherapy for locally advanced prostate and cervical cancer has been initiated, and preliminary results of the performance and heating distributions are reported herein. The treatment delivery platform consists of a 32 channel RF amplifier and a 48 channel thermocouple monitoring system. Controlling software can monitor and regulate frequency and power to each transducer section as required during the procedure. Interstitial applicators consist of multiple transducer sections of 2-4 cm length × 180 deg and 3-4 cm × 360 deg. heating patterns to be inserted in specific placed 13g implant catheters. The endocavity device, designed to be inserted within a 6 mm OD plastic tandem catheter within the cervix, consists of 2-3 transducers × dual 180 or 360 deg sectors. 3D temperature based treatment planning and optimization is dovetailed to the HDR optimization based planning to best configure and position the applicators within the catheters, and to determine optimal base power levels to each transducer section. To date we have treated eight cervix implants and six prostate implants. 100 % of treatments achieved a goal of >60 min duration, with therapeutic temperatures achieved in all cases. Thermal dosimetry within the hyperthermia target volume (HTV) and clinical target volume (CTV) are reported. Catheter-based ultrasound hyperthermia with HDR appears feasible with therapeutic temperature coverage of the target volume within the prostate or cervix while sparing surrounding more sensitive regions. (NIHR01CA122276).
Project description:Quality assurance (QA) guidelines are essential to provide uniform execution of clinical trials with uniform quality hyperthermia treatments. This document outlines the requirements for appropriate QA of all current superficial heating equipment including electromagnetic (radiative and capacitive), ultrasound, and infrared heating techniques. Detailed instructions are provided how to characterize and document the performance of these hyperthermia applicators in order to apply reproducible hyperthermia treatments of uniform high quality. Earlier documents used specific absorption rate (SAR) to define and characterize applicator performance. In these QA guidelines, temperature rise is the leading parameter for characterization of applicator performance. The intention of this approach is that characterization can be achieved with affordable equipment and easy-to-implement procedures. These characteristics are essential to establish for each individual applicator the specific maximum size and depth of tumors that can be heated adequately. The guidelines in this document are supplemented with a second set of guidelines focusing on the clinical application. Both sets of guidelines were developed by the European Society for Hyperthermic Oncology (ESHO) Technical Committee with participation of senior Society of Thermal Medicine (STM) members and members of the Atzelsberg Circle.
Project description:This paper proposes a hybrid hyperthermia treatment system, utilizing two noninvasive modalities for treating brain tumors. The proposed system depends on focusing electromagnetic (EM) and ultrasound (US) energies. The EM hyperthermia subsystem enhances energy localization by incorporating a multichannel wideband setting and coherent-phased-array technique. A genetic algorithm based optimization tool is developed to enhance the specific absorption rate (SAR) distribution by reducing hotspots and maximizing energy deposition at tumor regions. The treatment performance is also enhanced by augmenting an ultrasonic subsystem to allow focused energy deposition into deep tumors. The therapeutic faculty of ultrasonic energy is assessed by examining the control of mechanical alignment of transducer array elements. A time reversal (TR) approach is then investigated to address challenges in energy focus in both subsystems. Simulation results of the synergetic effect of both modalities assuming a simplified model of human head phantom demonstrate the feasibility of the proposed hybrid technique as a noninvasive tool for thermal treatment of brain tumors.
Project description:Interactions of high-frequency radio waves (RF) with biological tissues are currently being investigated as a therapeutic platform for non-invasive cancer hyperthermia therapy. RF delivers thermal energy into tissues, which increases intra-tumoral drug perfusion and blood-flow. Herein, we describe an optical-based method to optimize the short-term treatment schedules of drug and hyperthermia administration in a 4T1 breast cancer model via RF, with the aim of maximizing drug localization and homogenous distribution within the tumor microenvironment. This method, based on the analysis of fluorescent dyes localized into the tumor, is more time, cost and resource efficient, when compared to current analytical methods for tumor-targeting drug analysis such as HPLC and LC-MS. Alexa-Albumin 647?nm fluorphore was chosen as a surrogate for nab-paclitaxel based on its similar molecular weight and albumin driven pharmacokinetics. We found that RF hyperthermia induced a 30-40% increase in Alexa-Albumin into the tumor micro-environment 24?h after treatment when compared to non-heat treated mice. Additionally, we showed that the RF method of delivering hyperthermia to tumors was more localized and uniform across the tumor mass when compared to other methods of heating. Lastly, we provided insight into some of the factors that influence the delivery of RF hyperthermia to tumors.
Project description:The radiation of an electric dipole emitter can be drastically enhanced if the emitter is placed in the nano-gap of a metallic dipole antenna. By assuming that only surface plasmon polaritons (SPPs) are excited on the antenna, we build up an intuitive pure-SPP model that is able to comprehensively predict the electromagnetic features of the antenna radiation, such as the total or radiative emission rate and the far-field radiation pattern. With the model we can distinguish the respective contributions from SPPs and from other surface waves to the antenna radiation. It is found that for antennas with long arms that support higher-order resonances, SPPs provide a dominant contribution to the antenna radiation, while for other cases, the contribution of surface waves other than SPPs should be considered. The model reveals an intuitive picture that the enhancement of the antenna radiation is due to surface waves that are resonantly excited on the two antenna arms and that are further coupled into the nano-gap or scattered into free space. From the model we can derive a phase-matching condition that predicts the antenna resonance and the resultant enhanced radiation. The model is helpful for a physical understanding and intuitive design of antenna devices.
Project description:Microwave Ablation (MWA) is one of the most recent developments in the field of thermal therapy. This approach is an effective method for thermal tumor ablation by increasing the temperature above the normal physiological threshold to kill cancer cells with minimum side effects to surrounding organs due to rapid heat dispersive tissues. In the present study, the effects of the shape and size of the tumor on MWA are investigated. To obtain the temperature gradient, coupled bio-heat and electromagnetic equations are solved using a three-dimensional finite element method (FEM). To extract cellular response at different temperatures and times, the three-state mathematical model was employed to achieve the ablation zone size. Results show that treatment of larger tumors is more difficult than that of smaller ones. By doubling the diameter of the tumor, the percentage of dead cancer cells is reduced by 20%. For a spherical tumor smaller than 2 cm, applying 50 W input power compared to 25 W has no significant effects on treatment efficiency and only increases the risk of damage to adjacent tissues. However, for tumors larger than 2 cm, it can increase the ablation zone up to 21%. In the spherical and oblate tumors, the mean percentage of dead cells at 6 GHz is nearly 30% higher than that at 2.45GHz, but for prolate tumors, treatment efficacy is reduced by 10% at a higher frequency. Moreover, the distance between two slots in the coaxial double slot antenna is modified based on the best treatment of prolate tumors. The findings of this study can be used to choose the optimum frequency and the best antenna design according to the shape and size of the tumor.
Project description:Modulated electro-hyperthermia (mEHT) is a selective cancer treatment used in human oncology complementing other therapies. During mEHT, a focused electromagnetic field (EMF) is generated within the tumor, by elevated oxidative glycolysis (Warburg effect) and conductivity of the tumor. The EMF induce cell death by thermal and non-thermal effects. Here we investigated an aggressive, therapy resistant triple negative breast cancer (TNBC) model. 4T1/4T07 isografts inoculated orthotopically into female BALB/c mice were treated with mEHT 3-5 times. mEHT induced the upregulation of the stress related Hsp70 and cleaved caspase-3 proteins, resulting in effective inhibition of tumor growth and proliferation.
Project description:Breast cancer metastasis and disease recurrence are hypothesized to result from residual cancer stem cells, also referred to as tumor-initiating cells, which evade initial treatment. Using both syngeneic mouse and human xenograft models of triple-negative breast cancer, we have demonstrated that a subpopulation enriched in cancer stem cells was more resistant to treatment with 6 gray of ionizing radiation than the bulk of the tumor cells, and accordingly their relative proportion increased 48 to 72 hours after ionizing radiation treatment. In contrast, we achieved a larger reduction in tumor size without a concomitant increase in the percentage of cancer stem cells by treating with local hyperthermia for 20 minutes at 42°C after ionizing radiation using intravenously administered, optically activated gold nanoshells. Forty-eight hours after treatment, cells derived from the tumors treated with ionizing radiation plus hyperthermia exhibited both a marked decrease in tumorigenicity and a more differentiated phenotype than mock- and ionizing radiation-treated tumors. Thus, we have confirmed that these cancer stem cells are responsible for accelerated repopulation in vivo and demonstrated that hyperthermia sensitizes this cell population to radiation treatment. These findings suggest that local hyperthermia delivered by gold nanoshells plus radiation can eliminate radioresistant breast cancer stem cells.