Systematic review of pre-clinical and clinical devices for magnetic resonance-guided radiofrequency hyperthermia

Clinical trials have demonstrated the therapeutic benefits of adding radiofrequency (RF) hyperthermia (HT) as an adjuvant to radio- and chemotherapy. However, maximum utilization of these benefits is hampered by the current inability to maintain the temperature within the desired range. RF HT treatment quality is usually monitored by invasive temperature sensors, which provide limited data sampling and are prone to infection risks. Magnetic resonance (MR) temperature imaging has been developed to overcome these hurdles by allowing noninvasive 3D temperature monitoring in the target and normal tissues. To exploit this feature, several approaches for inserting the RF heating devices into the MR scanner have been proposed over the years. In this review, we summarize the status quo in MR-guided RF HT devices and analyze trends in these hybrid hardware configurations. In addition, we discuss the various approaches, extract best practices and identify gaps regarding the experimental validation procedures for MR - RF HT, aimed at converging to a common standard in this process

Radiofrequency applicator concepts for thermal magnetic resonance of brain tumors at 297 MHz (7.0 Tesla)

PURPOSE: Thermal intervention is a potent sensitizer of cells to chemo- and radiotherapy in cancer treatment. Glioblastoma multiforme (GBM) is a potential clinical target, given the cancer's aggressive nature and resistance to current treatment options. The annular phased array (APA) technique employing electromagnetic waves in the radiofrequency (RF) range allows for localized temperature increase in deep seated target volumes (TVs). Reports on clinical applications of the APA technique in the brain are still missing. Ultrahigh field magnetic resonance (MR) employs higher frequencies than conventional MR and has potential to provide focal temperature manipulation, high resolution imaging and noninvasive temperature monitoring using an integrated RF applicator (ThermalMR). This work examines the applicability of RF applicator concepts for ThermalMR of brain tumors at 297 MHz (7.0 Tesla). METHODS: Electromagnetic field (EMF) simulations are performed for clinically realistic data based on GBM patients. Two algorithms are used for specific RF energy absorption rate based thermal intervention planning for small and large TVs in the brain, aiming at maximum RF power deposition or RF power uniformity in the TV for 10 RF applicator designs. RESULTS: For both TVs , the power optimization outperformed the uniformity optimization. The best results for the small TV are obtained for the 16 element interleaved RF applicator using an elliptical antenna arrangement with water bolus. The two row elliptical RF applicator yielded the best result for the large TV. DISCUSSION: This work investigates the capacity of ThermalMR to achieve targeted thermal interventions in model systems resembling human brain tissue and brain tumors

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

Solving the time- and frequency-multiplexed problem of constrained radiofrequency induced hyperthermia

Targeted radiofrequency (RF) heating induced hyperthermia has a wide range of applications, ranging from adjunct anti-cancer treatment to localized release of drugs. Focal RF heating is usually approached using time-consuming nonconvex optimization procedures or approximations, which significantly hampers its application. To address this limitation, this work presents an algorithm that recasts the problem as a semidefinite program and quickly solves it to global optimality, even for very large (human voxel) models. The target region and a desired RF power deposition pattern as well as constraints can be freely defined on a voxel level, and the optimum application RF frequencies and time-multiplexed RF excitations are automatically determined. 2D and 3D example applications conducted for test objects containing pure water (r(target) = 19 mm, frequency range: 500–2000 MHz) and for human brain models including brain tumors of various size (r(1) = 20 mm, r(2) = 30 mm, frequency range 100–1000 MHz) and locations (center, off-center, disjoint) demonstrate the applicability and capabilities of the proposed approach. Due to its high performance, the algorithm can solve typical clinical problems in a few seconds, making the presented approach ideally suited for interactive hyperthermia treatment planning, thermal dose and safety management, and the design, rapid evaluation, and comparison of RF applicator configurations

Towards UWB 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 control in the thermal dose delivery which current systems are not able to provide. All clinical applicators available today are in fact based on a single-frequency technology. In terms of treatment planning options, 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 UWB systems opens up an opportunity to overcome these limitations, as they convey the possibility to adapt the focal spot and to use multiple operating frequencies to reduce the power deposition in healthy tissues.In this thesis, we explore whether the current treatment planning methods can be meaningfully translated to the UWB setting and propose new solutions for 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 cost-function specifically tailored for UWB optimization (HCQ). To solve for the HCQ, we further describe a novel, time-reversal based, iterative scheme for the rapid and efficient optimization of UWB treatment plans. We show that the combined use of these techniques results in treatment plans that better exploit the benefits of UWB systems, yielding increased tumor coverage and lower peak temperatures outside the target. Next, we investigate the design possibilities of UWB applicators and introduce a fast E-field approximation scheme. The method can be used for the global optimization of the array parameters with respect to the multiple objectives and requirements of hyperthermia treatments. Together, the proposed solutions represent a step forward in the implementation of patient-specific hyperthermia treatments, increasing their accuracy and precision. The results suggest that UWB microwave hyperthermia for brain cancer treatment is feasible, and motivate the efforts for further development of UWB applicators and systems

Magnetic resonance thermometry: methodology, pitfalls and practical solutions

Clinically established thermal therapies such as thermoablative approaches or adjuvant hyperthermia treatment rely on accurate thermal dose information for the evaluation and adaptation of the thermal therapy. Intratumoural temperature measurements have been correlated successfully with clinical end points. Magnetic resonance imaging is the most suitable technique for non-invasive thermometry avoiding complications related to invasive temperature measurements. Since the advent of MR thermometry two decades ago, numerous MR thermometry techniques have been developed, continuously increasing accuracy and robustness for in vivo applications. While this progress was primarily focused on relative temperature mapping, current and future efforts will likely close the gap towards quantitative temperature readings. These efforts are essential to benchmark thermal therapy efficiency, to understand temperature-related biophysical and physiological processes and to use these insights to set new landmarks for diagnostic and therapeutic applications. With that in mind, this review summarises and discusses advances in MR thermometry, providing practical considerations, pitfalls and technical obstacles constraining temperature measurement accuracy, spatial and temporal resolution in vivo. Established approaches and current trends in thermal therapy hardware are surveyed with respect to potential benefits for MR thermometry

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

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