Temperature Effects of Dielectric Properties and their Impact on Medical Device Development

Dielectric properties play an influential role in the development of medical devices. Understanding the behavior of these properties and how they respond to external stimuli, such as heat, over an extended frequency has yet to be researched. The focus of this study is to examine the impact of temperature on dielectric properties from 500 MHz to 10 GHz in order to better match the antenna properties of medical applications to the dielectric properties of biological tissue in question; more specifically, microwave ablation, microwave hyperthermia, and thermal modeling of brown adipose tissue’s metabolic processes. The dielectric properties of biological tissue samples from porcine lung, liver, heart, skin, fat, and muscle as well as brown adipose tissue and white adipose tissue from rat have been tested. These results have then been used to develop medical applications involving microwave antennas

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

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

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

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

Antenna and system design for controlled delivery of microwave thermal ablation

Doctor of PhilosophyDepartment of Electrical and Computer EngineeringPunit PrakashMicrowave ablation is an established minimally invasive modality for thermal ablation of unresectable tumors and other diseases. The goal of a microwave ablation procedure is to deliver microwave power in a manner localized to the targeted tissue, with the objective of raising the target tissue to ablative temperatures (~60 °C). Engineering efforts in microwave applicator design have largely been focused on the design of microwave antennas that yield large, near-spherical ablation zones, and can fit within rigid needles or flexible catheters. These efforts have led to significant progress in the development and clinical application of microwave ablation systems, particularly for treating tumors in the liver and other highly vascular organs. However, currently available applicator designs are ill-suited to treating targets of diverse shapes and sizes. Furthermore, there are a lack of non-imaging-based techniques for monitoring the transient progression of the ablation zone as a means for providing feedback to the physician. This dissertation presents the design, implementation, and experimental evaluation of microwave ablation antennas for site-specific therapeutic applications with these issues in mind. A deployable 915 MHz loop antenna is presented, providing a minimally-invasive approach for thermal ablation of the endometrial lining of the uterus for treatment of heavy menstrual bleeding. The antenna incorporates a radiating loop, which can be deployed to adjustable shapes within the uterine cavity, and a passive element, to enable thermal ablation, to 5.7–9.6 mm depth, of uterine cavities ranging in size from 4–6.5 cm in length and 2.5–4.5 cm in width. Electromagnetic–bioheat transfer simulations were employed for design optimization of the antennas, and proof-of-concept applicators were fabricated and extensively evaluated in ex vivo tissue. Finally, feasibility of using the broadband antenna reflection coefficient for monitoring the ablation progress during the course of ablation was evaluated. Experimental studies demonstrated a shift in antenna resonant frequency of 50 MHz correlated with complete ablation. For treatment of 1–2 cm spherical targets, water-cooled monopole antennas operating at 2.45 and 5.8 GHz were designed and experimentally evaluated in ex vivo tissue. The technical feasibility of using these applicators for treating 1–2 cm diameter benign adrenal adenomas was demonstrated. These studies demonstrated the potential of using minimally-invasive microwave ablation applicators for treatment of hypertension caused by benign aldosterone producing adenomas. Since tissue dielectric properties have been observed to change substantially at elevated temperatures, knowledge of the temperature-dependence of tissue dielectric properties may provide a means for estimating treatment state from changes in antenna reflection coefficient during a procedure. The broadband dielectric properties of bovine liver, an established tissue for experimental characterization of microwave ablation applicators, were measured from room temperature to ablative temperatures. The measured dielectric data were fit to a parametric model using piecewise linear functions, providing a means for readily incorporating these data into computational models. These data represent the first report of changes in broadband dielectric properties of liver tissue at ablative temperatures and should help enable additional studies in ablation system development

Entwicklung von RF-Technologie für die Ultrahochfeld-MRT: Optimierung und Anwendung einer Self-Grounded-Bow-Tie-Dipolantenne

Magnetic resonance imaging (MRI) is an important diagnostic imaging modality free of ionizing radiation. Sensitivity gain, signal-to-noise ratio (SNR) considerations, and changes in the tissue dependent MRI properties. Together with technical and scientific developments further research into increasing the magnetic field strength is justified, culminating in human applications at ultrahigh magnetic field (UHF, B0 ≥ 7.0 T) MRI. Elevating the field strength results in an increased radiofrequency (RF) for signal transmission and reception in MRI (= Larmor frequency, f ≈ 298 MHz at B0 = 7.0 T). The wavelength of this RF signal becomes sufficiently short when passing through tissue relative to the size of the target anatomy of the brain, upper torso, or abdomen. This phenomenon leads to constructive and deconstructive interference of the electromagnetic field (EMF) distribution, which results in a high susceptibility for non-uniformities in the magnetic RF transmission field (B1+). This detrimental excitation field distribution can cause shading, massive signal drop-off or even signal voids, and potentially offset the benefits of UHF-MRI due to compromised image quality. UHF cardiovascular MR (CMR) benefits from SNR gains and changes in the tissue dependent MRI properties, but the B1+ distribution – in addition to the wavelength dependent non-uniformities – is further compromised by a dielectrically heterogeneous tissue environment. Research on UHF-CMR focuses on the improvement of the cardiac chamber morphology quantification, myocardial T1- and T2*-mapping, fat-water imaging, and vascular imaging (4D-flow). These applications benefit from a homogenous B1+ within the heart and the vascular structure. Several published reports on the development of RF antenna array technology tailored for UHF-CMR address this challenge with ideas and achievements to enable broad clinical UHF-CMR applications in the future. The primary objective of advancing this RF technology is to achieve a uniform B1+ distribution in the heart and the vascular structure with optimizing the magnetic field pattern. The second objective is the improvement of the RF antenna’s efficiency with the reduction of the specific absorption rate (SAR), which is achieved by an optimization of the electric field pattern. The control of the electric field is furthermore conceptually appealing beyond conventional MR imaging modalities and useful for localized and targeted RF induced thermal intervention. Combining MRI with a thermal intervention modality in an integrated Thermal MR system permits direct supervision of the treatment via MR-thermometry, as well as adapting and improving the focal point quality of the RF power deposition. The Thermal MR system is a platform for comprehensive investigation of the effects of temperature on molecular, biochemical, and physiological processes, ultimately yielding insights into temperature utilization for diagnosis and therapy in vivo. EMF control of an RF antenna array depends on the radiation pattern of the antenna elements. Electrical dipoles are promising for UHF-MRI due to a linear polarized current pattern and an energy deposition perpendicular to the antenna. However, the channel count and therefore the degree of freedom for EMF shaping of previously reported antenna concepts is limited by the geometric extent and the coupling between the elements. The first section of this work addresses the design, implementation, and validation of a novel small-sized Self-Grounded Bow-Tie (SGBT) antenna, in combination with a dielectrically filled housing. The narrowband SGBT antenna variant is used in a 32-channel transmit/receive array configuration for UHF-CMR at 7.0 T. The second section focuses on the development of a modified broadband SGBT concept for the Thermal MR system. The broadband antenna increases the degree of freedom with an adaptation of the intervention frequency to improve the focal point quality (size, homogeneity, and specificity). The third section presents the implementation and validation of a signal generator in conjunction with the broadband SGBT variant introduced in section two. The device allows the generation of the intervention signal with a time dependent, channel-wise adaptation of amplitude, phase, and frequency. The work of this thesis offers a technical and conceptual framework for an increased degree of freedom for EMF shaping for a multitude of applications ranging from UHF-MRI to interventional MRI.Die Magnetresonanztomographie (MRI) ist ein wichtiges bildgebendes Diagnoseverfahren mit der Anwendung in vielen medizinischen Disziplinen. Die Forschung zu ultrahohen Magnetfeldern (UHF, B0 ≥ 7.0 T) im humanen Bereich wird durch technische und wissenschaftliche Errungenschaften getrieben und basiert auf einer höheren Sensitivität, einem verbesserten Signal-Rausch-Verhältnisses (SNR) sowie eine Veränderung der gewebsspezifischen MR Eigenschaften. Die höhere Feldstärke resultiert auch in einer erhöhten Radiofrequenz (RF) für die MRI Signalübertragung (= Larmorfrequenz, f ≈ 298 MHz bei B0 = 7.0 T). Die Wellenlänge des RF Signals im Gewebe ist dabei bezogen zur Zielanatomie (e.g. Schädel, Oberkörper und Abdomen) verkürzt was zu konstruktiven und destruktiven Interferenzen des elektromagnetischen Feldes (EMF) führt. Diese Interferenzen ergeben ein heterogenes RF Transmissionsfeld (B1+) mit Abschattungen, massiven Signalabfällen oder Signalausfällen welche die Vorteile der UHF-MRI durch eine beeinträchtigte Bildqualität schmälert. Die UHF Herz MR (CMR) profitiert von einem SNR-Gewinn sowie von veränderten gewebsspezifischen MR Eigenschaften bei höheren Feldstärken. Jedoch wird die B1+ Verteilung, neben der gegebenen RF wellenlängenabhängigen Heterogenität, durch dielektrische Gradienten im Bereich des Thorax zusätzlich beeinträchtigt. Die anwendungsbezogene Forschung und Entwicklung auf dem Gebiet der UHF-CMR konzentriert sich auf die Verbesserung der Quantifizierung der Herzkammermorphologie, des myokardialen T1- und T2*-Mappings, der Fett-Wasser-Bildgebung und der Gefäßbildgebung inklusive der Flussbildgebung (4D-Flow). Die Weiterentwicklung dieser Methoden streben eine breite klinische Anwendung an und profitieren von einer homogenen B1+ Verteilung im Herzen und in der Gefäßstruktur. Das primäre Ziel der der Forschung und Entwicklung von RF Antennenarraytechnologie ist eine Optimierung der B1+ Verteilung. Das sekundäre Ziel ist die Verbesserung der Effizienz durch die Verringerung der spezifischen Absorptionsrate (SAR) mittels einer elektrischen Feldoptimierung. Die Kontrolle des elektrischen Feldes kann aber auch über die konventionelle MR Bildgebung hinaus genutzt werden und ermöglicht konzeptionell eine lokalisierte und gezielte RF induzierte thermische Intervention. Die Kombination von MRI und thermischen Interventionen in einem integrierten Thermal MR System ermöglicht die Anpassung und Verbesserung der lokalen Intervention durch eine Supervision der Behandlung mittels MR-Thermometrie. Das Thermal MR System stellt damit eine technologische Plattform dar, welche eine umfassende Untersuchung der Auswirkungen der Temperatur auf molekulare, biochemische und physiologische Prozesse erlaubt. Letztlich kann die Plattform Erkenntnisse darüber liefern, wie die Temperatur für Diagnosen und Therapien in vivo genutzt werden kann. Die Kontrolle der EMF Verteilung durch ein RF Antennen Array ist abhängig von den Abstrahlungseigenschaften der einzelnen Antennenelemente. Elektrische Dipole stellen durch eine linear polarisierte Stromverteilung und eine Abstrahlungsrichtung orthogonal zur Antenne eine vielversprechende Option dar. Allerdings ist die Kanalzahl und damit der Freiheitsgrad für die EMF Optimierung bei bisher vorgestellten Antennenkonzepten durch die Größe und die Kopplung zwischen den Elementen begrenzt. Der erste Abschnitt dieser Arbeit befasst sich mit dem Entwurf, der Implementierung und der Validierung einer Self-Grounded Bow-Tie (SGBT) Antenne in Kombination mit einem dielektrisch gefüllten Gehäuse. Eine schmalbandige Antennenvariante wird in einer 32-Kanal Sende-/Empfangs-Array Konfiguration für UHF-CMR bei 7,0 T vorgestellt. Der zweite Abschnitt befasst sich mit der Entwicklung eines modifizierten breitbandigen SGBT-Konzepts für das Thermal MR System. Diese Antennenvariante erhöht die Freiheitsgrade für die Optimierung der elektrischen Feldverteilung um die Interventionsfrequenz und erlaubt eine Verbesserung der lokalen Erwärmung (Größe, Homogenität und Spezifität). Im dritten Abschnitt dieser Arbeit wird die Implementierung und Validierung eines Signalgenerators in Verbindung mit der im zweiten Abschnitt vorgestellten Breitbandantennenvariante vorgestellt. Der Signalgenerator erzeugt einen Interventionssignal mit der zeitabhängigen Anpassung von Amplitude, Phase und Frequenz für jeden Kanal. Die Entwicklungen und Erkenntnisse dieser Arbeit bieten einen konzeptionellen Rahmen für eine Vielzahl von realen Anwendungen, welche von der konventionellen MRI bis zu einem integrierten interventionellen Thermal MR System reichen.EC/H2020/743077/EU/Thermal Magnetic Resonance: A New Instrument to Define the Role of Temperature in Biological Systems and Disease for Diagnosis and Therapy/ThermalM

Anniversary Paper: Evolution of ultrasound physics and the role of medical physicists and the AAPM and its journal in that evolution

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134810/1/mp2048.pd

Radiobiological evaluation of combined gamma knife radiosurgery and hyperthermia for pediatric neuro-oncology

Combining radiotherapy (RT) with hyperthermia (HT) has been proven effective in the treatment of a wide range of tumours, but the combination of externally delivered, focused heat and stereotactic radiosurgery has never been investigated. We explore the potential of such treatment enhancement via radiobiological modelling, specifically via the linear-quadratic (LQ) model adapted to thermoradiotherapy through modulating the radiosensitivity of temperature-dependent parame-ters. We extend this well-established model by incorporating oxygenation effects. To illustrate the methodology, we present a clinically relevant application in pediatric oncology, which is novel in two ways. First, it deals with medulloblastoma, the most common malignant brain tumour in children, a type of brain tumour not previously reported in the literature of thermoradiotherapy studies. Second, it makes use of the Gamma Knife for the radiotherapy part, thereby being the first of its kind in this context. Quantitative metrics like the biologically effective dose (BED) and the tumour control probability (TCP) are used to assess the efficacy of the combined plan

Image-guidance and computational modeling to develop and characterize microwave thermal therapy platforms

Doctor of PhilosophyDepartment of Electrical and Computer EngineeringPunit PrakashThis dissertation focuses on the development of magnetic resonance imaging (MRI)-guided microwave thermal therapy systems for driving experimental studies in small animals, and to experimentally validate computational models of microwave ablation, which are widely employed for device design and characterization. MRI affords noninvasive monitoring of spatial temperature profiles, thereby providing a means to to quantitatively monitor and verify delivery of prescribed thermal doses in experimental studies and clinical use, as well as a means to validate thermal profiles predicted by computational models of thermal therapy. A contribution of this dissertation is the development and demonstration of a system for delivering mild hyperthermia to small animal targets, thereby providing a platform for driving basic research studies investigating the use of heating as part of cancer treatment strategies. An experimentally validated 3D computational model was employed to design and characterize a non-invasive directional water-cooled microwave hyperthermia applicator for MRI guided delivery of hypethermia in small animals. Following a parametric model-based design approach, a reflector aperture angle of 120°, S-shaped monopole antenna with 0.6 mm displacement, and a coolant flow rate of 150 ml/min were selected as applicator parameters that enable conformal delivery of mild hyperthermia to tumors in experimental animals. The system was integrated with real-time high-field 14.1 T MRI thermometry and feedback control to monitor and maintain target temperature elevations in the range of 4 – 5 °C (hypethermic range). 2 - 4 mm diameter targets positioned 1 – 3 mm from the applicator surface were heated to hyperthermic temperatures, with target coverage ratio ranging between 76 - 93 % and 11 – 26 % of non-targeted tissue heated. Another contribution of this dissertation is using computational models to determine how the fibroids altered ablation profile of a microwave applicator for global endometrial ablation. Uterine fibroids are benign pelvic tumors located within the myometrium or endometrium,and may alter the profile of microwave ablation applicators deployed within the uterus for delivering endometrial ablation. A 3D computational model was employed to investigate the effect of 1 – 3 cm diameter uterine fibroids in different locations around the uterine cavity on endometrial ablation profiles of microwave exposure with a 915 MHz microwave triangular loop antenna. The maximum change in simulated ablation depths due to the presence of fibroids was 1.1 mm. In summary, this simulation study suggests that 1 – 3 cm diameter uterine fibroids can be expected to have minimal impact on the extent of microwave endometrial ablation patterns achieved with the applicator studied in this dissertation. Another contribution of this dissertation is the development of a method for experimental validation of 3D transient temperature profiles predicted by computational models of MWA. An experimental platform was developed integrating custom designed MR-conditional MWA applicators for use within the MR environment. This developed platform was employed to conduct 30 - 50 W, 5 - 10 min MWA experiments in ex vivo tissue. Microwave ablation computational models, mimicking the experimental setting in MRI, were implemented using the finite element method, and incorporated temperature-dependent changes in tissue physical properties. MRI-derived Arrhenius thermal damage maps were compared to Model-predicted ablation zone extents using the Dice similarity coefficient (DSC). Mean absolute error between MR temperature measurements and fiber-optic temperature probes, used to validate the accuracy of MR temperature measurements, during heating was in the range of 0.5 – 2.8 °C. The mean DSC between model-predicted ablation zones and MRI-derived Arrhenius thermal damage maps for 13 experimental set-ups was 0.95. When comparing simulated and experimentally (i.e. using MRI) measured temperatures, the mean absolute error (MAE %) relative to maximum temperature change was in the range 5 % - 8.5 %