Modeling the SIGMA-Eye Applicator for Hyperthermia via Multiple Infinitesimal Dipoles

Over the past several decades, cancer is still one of the leading causes of human deaths. Hyperthermia treatment, which is mostly performed in clinic as an assistant therapy method combined with chemotherapy or radiation therapy, has been also playing a more and more important role in tumor therapy. Driven by the developments of computing power and computational techniques, personalized hyperthermia treatment planning (HTP) is becoming possible and essential for clinical practice, aimed at achieving maximum treatment effects for tumor targets and minimal side effects for the surrounding tissues simultaneously. As an essential step of Electromagnetic Hyperthermia Treatment Planning, electromagnetic simulation with the phased-array applicator, SIGMA-Eye hyperthermia applicator, was explored. The approach of the basic-building-block-based modified Infinitesimal Dipole Model (IDM) as a virtual source model was developed and used for modeling the hyperthermia SIGMA-Eye applicator (BSD Medical Corporation) in this work. The basic idea of the IDM [1] is to replace the antenna with a series of infinitesimal dipoles which generates the same electric field as the antenna does. On the basis of the conventional IDM, a modified IDM is proposed, in which number and locations of dipoles are predefined. The reduced set of dipole parameters leads to a simpler objective function of the modified IDM in comparison to the conventional IDM concerning parameter fitting. In addition, the concept of a ‘basic building block’ [2] is introduced: the antenna under test (active antenna) and its neighboring antenna elements (passive antennas) are considered as a basic building block. The dipole model of the antenna under test will be fit by approximating the electric field of the block in order to correctly treat the mutual coupling between antenna elements. Therefore, electric fields generated by a phased-array applicator (with significant mutual coupling between elements) can be modeled. In this work, each antenna of the SIGMA-Eye applicator was modelled using the basic-building-block-based modified IDM. Taking the electric field data of the basic building block computed from the software COMSOL Multiphysics as reference, the global optimization algorithm OQNLP (OptQuest Nonlinear Programming) [3] was used for parameter fitting of the dipole models. And then the SIGMA-Eye applicator was simulated by the superposition of each simulated antenna. Electromagnetic simulations with different phase combinations of the antenna elements of the applicator were performed. The resulted electromagnetic energy deposition patterns were compared to the measurement data presented in the reference paper [4], where the electric field measurement within the phantom placed inside the SIGMA-Eye applicator was performed. The relative differences of energy deposition patterns ranged from 1.40% to 17.90% with an average at 5.07%. The agreement of energy deposition patterns between simulation data and measurement data justified the applicability of our virtual source model to hyperthermia forward planning and further to the commissioning of new systems. In addition, the frequency dependence and water-bolus permittivity and conductivity dependence of the block-based modified IDM was explored, and it was found that this approach is applicable for a narrow-band frequency, and is adaptable to the uncertainty of the water-bolus permittivity and conductivity. When operating at a frequency further away from the reference frequency, or the surrounding environment of the antennas changes a lot, the applicator needs to be simulated using a new equivalent model. [1] Mikki, S.M. and A.A. Kishk, Theory and applications of infinitesimal dipole models for computational electromagnetics. Ieee Transactions on Antennas and Propagation, 2007. 55(5): p. 1325-1337. [2] Mikki, S.M. and Y.M.M. Antar, Near-Field Analysis of Electromagnetic Interactions in Antenna Arrays Through Equivalent Dipole Models. Ieee Transactions on Antennas and Propagation, 2012. 60(3): p. 1381-1389. [3] Ugray, Z., Lasdon, L., Plummer, J., Glover, F., Kelly, J. and Martí, R, Scatter Search and Local NLP Solvers: A Multistart Framework for Global Optimization. INFORMS Journal on Computing, 2007. 19(3): p. 328-340. [4] F.Turner, P., Technical Aspect of the BSD-2000 and BSD-2000∙3D, in European Society for Hyperthermia Oncology and BSD Medical Corporation User’s Conference. 1997

ESHO benchmarks for computational modeling and optimization in hyperthermia therapy

Background: The success of cancer hyperthermia (HT) treatments is strongly dependent on the temperatures achieved in the tumor and healthy tissues as it correlates with treatment efficacy and safety, respectively. Hyperthermia treatment planning (HTP) simulations have become pivotal for treatment optimization due to the possibility for pretreatment planning, optimization and decision making, as well as real-time treatment guidance. Materials and methods: The same computational methods deployed in HTP are also used for in silico studies. These are of great relevance for the development of new HT devices and treatment approaches. To aid this work, 3 D patient models have been recently developed and made available for the HT community. Unfortunately, there is no consensus regarding tissue properties, simulation settings, and benchmark applicators, which significantly influence the clinical relevance of computational outcomes. Results and discussion: Herein, we propose a comprehensive set of applicator benchmarks, efficacy and safety optimization algorithms, simulation settings and clinical parameters, to establish benchmarks for method comparison and code verification, to provide guidance, and in view of the 2021 ESHO Grand Challenge (Details on the ESHO grand challenge on HTP will be provided at https://www.esho.info/). Conclusion: We aim to establish guidelines to promote standardization within the hyperthermia community such that novel approaches can quickly prove their benefit as quickly as possible in clinically relevant simulation scenarios. This paper is primarily focused on radiofrequency and microwave hyperthermia but, since 3 D simulation studies on heating with ultrasound are now a reality, guidance as well as a benchmark for ultrasound-based hyperthermia are also included

Antenna Design, Radiobiological Modelling, and Non-invasive Monitoring for Microwave Hyperthermia

The death toll of cancers is on the rise worldwide and surviving patients suffer significant side effects from conventional therapies. To reduce the level of toxicity in patients treated with the conventional treatment modalities, hyperthermia (HT) has been investigated as an adjuvant modality and shown to be a potent tumor cell sensitizer for radio- and chemotherapy. During the past couple of decades, several clinical radiofrequency HT systems, aka applicators, have been developed to heat tumors. Systems based on radiative applicators are the most widely used within the hyperthermic community. They consist of a conformal antenna array and need a beamforming method in order to focus EM energy on the tumor through constructive interference while sparing the healthy tissue from excessive heating. Therefore, a hyperthermia treatment planning (HTP) stage is required before each patient\u27s first treatment session to optimize and control the EM power deposition as well as the resultant temperature distribution. Despite the vast amount of effort invested in HTP and the progress made in this regard during recent years, the clinical exploitation of HT is still hampered by technical limitations and patients can still experience discomfort during clinical trials. This, therefore, calls for a more efficient hardware design, better control of EM power deposition to minimize unwanted hotspots, and more accurate quantification and monitoring of the treatment outcome. Given these demands, the present report tries to address some of the above-mentioned challenges by proposing - A new antenna model customized for HT applications that surpasses previously proposed models from several points of view.- A hybrid beamforming method for faster convergence and a versatile, robust thermal solver for handling sophisticated scenarios.- A radiobiological model to quantify the outcome of a combined treatment modality of the Gamma Knife radiosurgery and HT.- A differential image reconstruction method to assess the feasibility of using the same system for both heating and microwave thermometry

Optimizing microwave hyperthermia antenna systems

This thesis presents design and optimization of a microwave hyperthermia antennasystem for treatment of head and neck cancer as well as brain cancer. Hyperthermiahas shown the ability to enhance the performance of radiotherapy andchemotherapy in many clinical trials. The incidence of increased tissue toxicity asa result of high radiotherapy dose has made hyperthermia a safe complementing,treatment enhancing method to use in combination with radiotherapy. Althoughmany clinical studies have shown the effectiveness of hyperthermia for treatmentof the head-and-neck (H&N) cancer, the presence of large vessels, tissue transitionsand critical tissues in the head and neck poses therapeutic challenges fortreatment of advanced tumors in this region. Late side-effects of conventionaltherapies in treatment of brain tumors in children have been made hyperthermiaan attractive method. However, heating tumors in the brain is even more challengingbecause of its high sensitivity, high thermal conductivity and high perfusion.In this thesis microwave hyperthermia applicators are presented for efficientheating of the H&N and brain tumors. For this purpose, an ultra-wideband antennahas been designed, built and evaluated to act as the radiating element of microwavehyperthermia applicators. The time reversal focusing technique is used totarget electromagnetic energy into the tumor. To obtain more accurate treatmentplanning, the effect of frequency and virtual source positions, in the time-reversalmethod, are studied for different tumor sizes and tumor positions. The optimaldetailed design of the applicator, such as the number of antennas and the antennapositions are also investigated.In the second part of the thesis, the focus is on the applicators for treatment ofthe brain tumors in children. Helmet applicators are presented and the effect of thenumber of antennas and the frequency are investigated on the performance of theapplicators for heating large and deep-seated brain tumors. Finally, the optimumposition of antennas in helmet applicators are found by performing optimizationon simplified and realistic models of the child head

Ultra wideband microwave hyperthermia for brain cancer treatment

Despite numerous clinical trials demonstrating that microwave hyperthermia is a powerful adjuvant modality in the treatment of cancers, there have been few instances where this method has been applied to brain tumors. The reason is a combination of anatomical and physiological factors in this site that require an extra degree of accuracy and precision in the thermal dose delivery. Current clinical applicators are not able to provide such control, partly because they are designed to operate at a single fixed frequency. In terms of treatment planning, the use of a single frequency is limiting as the size of the focal spot cannot be modified to accommodate the specific tumor volume and location. The introduction of ultra wide-band (UWB) systems opens up an opportunity to overcome these limitations, as they convey the possibility of adapting the focal spot and obtaining different power deposition patterns to reduce the heating of healthy tissues.In this thesis, we explore whether the current SAR-based treatment planning methods can be meaningfully translated to the UWB setting and propose new solutions for deep UWB microwave hyperthermia. We analyze the most commonly used cost functions for treatment planning optimization and discuss their suitability for use with UWB systems. Then, we propose a novel SAR-based cost function (HCQ) for UWB optimization that exhibits a high correlation with the resulting tumor temperature. To solve for the HCQ, we describe a novel, time-reversal-based, iterative scheme for a rapid and efficient optimization of UWB treatment plans. Next, we investigate the design possibilities of UWB brain applicators and introduce a fast E-field approximation scheme to quickly explore a large number of array configurations. The method determines the best antenna arrangement around the head with respect to the multiple objectives and requirements of clinical hyperthermia. Together, the proposed solutions manage to achieve the level of tumor coverage and hot-spot suppression that is necessary for a successful treatment. Finally, we investigate the benefit of integrating hyperthermia delivered by an optimized UWB applicator into the radiation therapy plan for a pediatric medulloblastoma patient. The results suggest that UWB microwave hyperthermia for brain cancer treatment is feasible and motivate efforts for further development of UWB applicators and systems

Target-specific multiphysics modeling for thermal medicine applications

Dissertation to obtain the degree of Doctor of Philosophy in Biomedical EngineeringThis thesis addresses thermal medicine applications on murine bladder hyperthermia and brain temperature monitoring. The two main objectives are interconnected by the key physics in thermal medicine: heat transfer. The first goal is to develop an analytical solution to characterize the heat transfer in a multi-layer perfused tissue. This analytical solution accounts for important thermoregulation mechanisms and is essential to understand the fundamentals underlying the physical and biological processes associated with heat transfer in living tissues. The second objective is the development of target-specific models that are too complex to be solved by analytical methods. Thus, the software for image segmentation and model simulation is based on numerical methods and is used to optimize non-invasive microwave antennas for specific targets. Two examples are explored using antennas in the passive mode (probe) and active mode (applicator). The passive antenna consists of a microwave radiometric sensor developed for rapid non-invasive feedback of critically important brain temperature. Its design parameters are optimized using a power-based algorithm. To demonstrate performance of the device, we build a realistic model of the human head with separate temperaturecontrolled brain and scalp regions. The sensor is able to track brain temperature with 0.4 °C accuracy in a 4.5 hour long experiment where brain temperature is varied in a 37 °C, 27 °C and 37 °C cycle. In the second study, a microwave applicator with an integrated cooling system is used to develop a new electro-thermo-fluid (multiphysics) model for murine bladder hyperthermia studies. The therapy procedure uses a temperature-based optimization algorithm to maintain the bladder at a desired therapeutic level while sparing remaining tissues from dangerous temperatures. This model shows that temperature dependent biological properties and the effects of anesthesia must be accounted to capture the absolute and transient temperature fields within murine tissues. The good agreement between simulation and experimental results demonstrates that this multiphysics model can be used to predict internal temperatures during murine hyperthermia studies

Recent technological advancements in radiofrequency- andmicrowave-mediated hyperthermia for enhancing drug delivery

Hyperthermia therapy is a potent enhancer of chemotherapy and radiotherapy. In particular, microwave (MW) and radiofrequency (RF) hyperthermia devices provide a variety of heating approaches that can treat most cancers regardless the size. This review introduces the physics of MW/RF hyperthermia, the current state-of-the-art systems for both localized and regional heating, and recent advancements in hyperthermia treatment guidance using real-time computational simulations and magnetic resonance thermometry. Clinical trials involving RF/MW hyperthermia as adjuvant for chemotherapy are also presented per anatomical site. These studies favor the use of adjuvant hyperthermia since it significantly improves curative and palliative clinical outcomes. The main challenge of hyperthermia is the distribution of state-of-the-art heating systems. Nevertheless, we anticipate that recent technology advances will expand the use of hyperthermia to chemotherapy centers for enhanced drug delivery. These new technologies hold great promise not only for (image-guided) perfusion modulation and sensitization for cytotoxic drugs, but also for local delivery of various compounds using thermosensitive liposomes

Heating technology for malignant tumors: a review

The therapeutic application of heat is very effective in cancer treatment. Both hyperthermia, i.e., heating to 39-45 degrees C to induce sensitization to radiotherapy and chemotherapy, and thermal ablation, where temperatures beyond 50 degrees C destroy tumor cells directly are frequently applied in the clinic. Achievement of an effective treatment requires high quality heating equipment, precise thermal dosimetry, and adequate quality assurance. Several types of devices, antennas and heating or power delivery systems have been proposed and developed in recent decades. These vary considerably in technique, heating depth, ability to focus, and in the size of the heating focus. Clinically used heating techniques involve electromagnetic and ultrasonic heating, hyperthermic perfusion and conductive heating. Depending on clinical objectives and available technology, thermal therapies can be subdivided into three broad categories: local, locoregional, or whole body heating. Clinically used local heating techniques include interstitial hyperthermia and ablation, high intensity focused ultrasound (HIFU), scanned focused ultrasound (SFUS), electroporation, nanoparticle heating, intraluminal heating and superficial heating. Locoregional heating techniques include phased array systems, capacitive systems and isolated perfusion. Whole body techniques focus on prevention of heat loss supplemented with energy deposition in the body, e.g., by infrared radiation. This review presents an overview of clinical hyperthermia and ablation devices used for local, locoregional, and whole body therapy. Proven and experimental clinical applications of thermal ablation and hyperthermia are listed. Methods for temperature measurement and the role of treatment planning to control treatments are discussed briefly, as well as future perspectives for heating technology for the treatment of tumors

マイクロ波温熱と放射線近接照射の組み合わせによる、乳がん向け治療法の検討

学位の種別: 課程博士審査委員会委員 : （主査）東京大学教授 上坂 充, 東京大学教授 高橋 浩之, 東京大学准教授 関野 正樹, 東京医科歯科大学教授 中島 義和, 千葉大学准教授 齊藤 一幸, 千葉大学客員教授 伊藤 公一University of Tokyo(東京大学