Quality assurance guidelines for superficial hyperthermia clinical trials: II. Technical requirements for heating devices

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

Wide Band Embedded Slot Antennas for Biomedical, Harsh Environment, and Rescue Applications

For many designers, embedded antenna design is a very challenging task when designing embedded systems. Designing Antennas to given set of specifications is typically tailored to efficiently radiate the energy to free space with a certain radiation pattern and operating frequency range, but its design becomes even harder when embedded in multi-layer environment, being conformal to a surface, or matched to a wide range of loads (environments). In an effort to clarify the design process, we took a closer look at the key considerations for designing an embedded antenna. The design could be geared towards wireless/mobile platforms, wearable antennas, or body area network. Our group at UT has been involved in developing portable and embedded systems for multi-band operation for cell phones or laptops. The design of these antennas addressed single band/narrowband to multiband/wideband operation and provided over 7 bands within the cellular bands (850 MHz to 2 GHz). Typically the challenge is: many applications require ultra wide band operation, or operate at low frequency. Low frequency operation is very challenging if size is a constraint, and there is a need for demonstrating positive antenna gain

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

Analysis of clinical data to determine the minimum number of sensors required for adequate skin temperature monitoring of superficial hyperthermia treatments

Purpose: Tumor response and treatment toxicity are related to minimum and maximum tissue temperatures during hyperthermia, respectively. Using a large set of clinical data, we analyzed the number of sensors required to adequately monitor skin temperature during superficial hyperthermia treatment of breast cancer patients. Methods: Hyperthermia treatments monitored with >60 stationary temperature sensors were selected from a database of patients with recurrent breast cancer treated with re-irradiation (23 7 2 Gy) and hyperthermia using single 434 MHz applicators (effective field size 351–396 cm2). Reduced temperature monitoring schemes involved randomly selected subsets of stationary skin sensors, and another subset simulating continuous thermal mapping of the skin. Temperature differences (ΔT) between subsets and complete sets of sensors were evaluated in terms of overall minimum (Tmin) and maximum (Tmax) temperature, as well as T90 and T10. Results: Eighty patients were included yielding a total of 400 hyperthermia sessions. Median ΔT was 50 sensors were used. Subsets of 50 sensors were used. Thermal profiles (8–21 probes) yielded a median ΔT < 0.01 \ub0C for T90 and Tmax, with a 95%CI of −0.2 \ub0C and 0.4 \ub0C, respectively. The detection rate of Tmax≥43 \ub0C is ≥85% while using >50 stationary sensors or thermal profiles. Conclusions: Adequate coverage of the skin temperature distribution during superficial hyperthermia treatment requires the use of >50 stationary sensors per 400 cm2applicator. Thermal mapping is a valid alternative

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

Antenna Development for Radio Frequency Hyperthermia Applications

This thesis deals with the design steps, development and validation of an applicator for radio frequency hyperthermia cancer therapy. An applicator design to enhance targeted energy coupling is a key enabler for preferential temperature increments in tumour regions. A single-element, near-field approach requires a miniaturised solution, that addresses ergonomic needs and is tolerant to patient anatomy. The antenna war-field rriodality and the high-dielectric patient loading introduce significant analytical and computational resource challenges. The antenna input impedance has to be sufficiently insensitive to in-band resonant cletuning and the fields in the tissue can he targeted to selected areas in the patient. An introduction to the medical and biological background of hyperthermia is presented. The design requirements of antennas for medical and in particular for hyperthermia applications are highlighted. Starting from a conventional circular patch, the antenna evolved into a compact circular patch with a concentric annular ring and slotted groundplane, operating at the 434 MHz Industrial Scientific and Medical frequency band. Feed point location is optimized for an energy deposition pattern aligned with the antenna centre. The applicator is assessed with other published approaches and clinically used loop, dipole and square patch antennas. The antennas are evaluated for the unloaded condition and when loaded with a tri-layer body tissue numerical model. This model comprises skin, fat and transverse fiber of muscle of variable thicknesses to account for different body locations and patient. anatomy. A waterbolus containing de-ionized water is added at the skin interface for superficial tissue cooling aud antelina matching. The proposed applicator achieves a penetration depth that supersedes other approaches while remaining compact and an ergonomic fit to tumour areas on the body. To consider the inner and peripheral complex shapes of human bodies, the full human body numerical model developed by Remcom is used. This model was segmented from 1 mm step computed tomography (CT) and magnetic resonance imaging (MRI) cross-sections through and adult male and it comprises twenty-three tissue types with thermal and frequency-dependent dielectric properties. The applicator performance is evaluated at three anatomical body areas of the model to assess its suitability for treatment of tumours at different locations. These three anatomical regions present different aperture coupling and tissue composition. \u27Different conformal waterbolus and air gap thickness values are evaluated. The models used in this work are validated with measurements performed in a phantom containing a lossy liquid with dielectric properties representative of homogeneous human body tissue. The dosimetric assessment system (DASY) is used to evaluaxe the specific absorption rate (SAR) generated for the antenna into the liquid. The measurement setup with the antenna, phantom and liquid are simulated. Simulated and measured results in terrms of specific absorption rate and return loss are evaluated

Measurement and mathematical modeling of hyperthermia induced bioeffects in pancreatic cancer cells

Doctor of PhilosophyDepartment of Electrical and Computer EngineeringPunit PrakashSurgical resection is the standard of care for pancreatic cancer, although treatment outcomes remain poor, and a large fraction of the patient population are not surgical candidates. Minimally invasive interventions employing non-ionizing energy, such as image-guided thermal ablation, are under investigation for treatment of unresectable tumors and potentially for debulking and downstaging tumors. Tissue regions at the periphery of an ablation zone are exposed to sub-ablative thermal profiles (referred to as “mild hyperthermia”), which may induce a range of bioeffects including change in perfusion, immune modulation, and others. Bioeffects induced by heating are a function of intensity of heating and duration of thermal exposure. This dissertation presents a suite of tools for integrated in vitro experimental studies and modeling for characterizing bioeffects following thermal exposure to pancreatic cancer cells. An instrumentation platform was developed for exposing monolayer cell cultures to temperatures in the range 42–50°C for 3–60 minutes. The platform was employed to determine the Arrhenius kinetic parameters of thermal injury to pancreatic cancer cells (i.e. loss in viability) following heating. When coupled with bioheat transfer models, these parameters facilitate investigations of thermal injury profiles in pancreatic tumors following thermal exposure with practical devices. There has been growing interest in exploring the potential of thermal therapies for modulating tumor—immune system interactions, due in part to release of damage associated molecular patterns (DAMPs) from stressed tumor cells and their role in recruiting and activating antigen presenting cells. The in vitro thermal exposure platform was further expanded to allow for experimental measurement of extracellular DAMPs released from murine pancreatic cancer cells following heating to temperatures in the range 42 – 50°C for 3-60 mins. A model predicting the dynamics of heat-induced DAMPs release was developed and may inform the design of experiments investigating the role of heat in modulating the anti-tumor immune response. While in vitro experiments on monolayers are informative, 3D cell cultures (e.g., spheroid, organoids) provide an experimental platform accommodating multiple cell types in an environment that may be more representative of tumors in vivo. Furthermore, while the water-bath based in vitro platform applied for monolayers is well suited to achieving near-uniform temperature profiles, in vivo delivery of hyperthermia often yields a gradient of temperatures that is not achieved through water-bath based heating. Thus, an in vitro platform for exposing cells in 3D culture (co-culture of multiple cell populations) to 2.45 GHz microwave hyperthermia was developed. The platform includes a printed patch antenna and associated thermal management elements and was applied to study changes in gene expression profile of a 3D culture of pancreatic cancer cells and fibroblasts. This non-contact microwave heating approach may help enable additional studies for exploring the bioeffects of heat on cancer cells