Two-compartment mathematical modeling in RF tumor ablation: New insight when irreversible changes in electrical conductivity are considered

[EN] The objective was to explore variations of temperature distribution and coagulation zone size computed by a two-compartment radiofrequency ablation (RFA) model when including simultaneously reversible changes in the tissue electrical conductivity (sigma) due to temperature and irreversible changes due to thermal coagulation. Two-compartment (tumor and healthy tissue) models were built and simulated. Reversible change of sigma was modeled by a piecewise function characterized by increments of +1.5%/degrees C up to 100 degrees C, and a 100 times smaller value from 100 degrees C onwards. Irreversible changes of sigma were modeled using an Arrhenius model. We assumed that both tumor and healthy tissue had a different initial sigma value (as suggested by the experimental data in the literature) and tended towards a common value as thermal damage progressed (necrotized tissue). We modeled a constant impedance protocol based on 90 V pulses voltage and three tumor diameters (2, 3 and 4 cm). Computer simulations showed that the differences between both models were only 0.1 and 0.2 cm for axial and transverse diameters, respectively, and this small difference was reflected in the similar temperature distributions computed by both models. In view of the available experimental data on changes of electrical conductivity in tumors and healthy tissue during heating, our results suggest that irreversible changes in electrical conductivity do not have a significant impact on coagulation zone size in two-compartment RFA models.This work was supported by the National Council of Science and Technology (CONACYT, Mexico) through a scholarship grant to Dora Luz Castro-Lopez, CVU registration No 446604; and by the Spanish Ministerio de Ciencia, Innovacion y Universidades under "Programma Estatal de I+D+i Orientada a los Retos de la Sociedad", Grant No "RTI2018-094357-B-C21".Castro-López, DL.; Trujillo Guillen, M.; Berjano, E.; Romero-Mendez, R. (2020). Two-compartment mathematical modeling in RF tumor ablation: New insight when irreversible changes in electrical conductivity are considered. Mathematical Biosciences and Engineering. 17(6):7980-7993. https://doi.org/10.3934/mbe.2020405S798079931762. D. Haemmerich, L. Chachati, A. S. Wright, D. M. Mahvi, F. T. Lee Jr, J. G. Webster, Hepatic radiofrequency ablation with internally cooled probes: Effect of coolant temperature on lesion size, IEEE Trans. Biomed. Eng., 50 (2003), 493-500.4. Z. Liu, S. M. Lobo, S. Humphries, C. Horkan, S. A. Solazzo, A. U. Hines-Peralta, et al., Radiofrequency tumor ablation: insight into improved efficacy using computer modeling, AJR Am. J. Roentgenol., 184 (2005), 1347-1352.5. S. M. Lobo, Z. J. Liu, N. C. Yu, S. Humphries, M. Ahmed, E. R. Cosman, et al., RF tumour ablation: computer simulation and mathematical modelling of the effects of electrical and thermal conductivity, Int. J. Hyperth., 21 (2005), 199-213.9. D. Haemmerich, D. J. Schutt, RF ablation at low frequencies for targeted tumor heating: In vitro and computational modeling results, IEEE Trans. Biomed. Eng., 58 (2011), 404-410.17. M. Pop, A. Molckovsky, L. Chin, M. C. Kolios, M. A. Jewett, M. D. Sherar, Changes in dielectric properties at 460 kHz of kidney and fat during heating: importance for radio-frequency thermal therapy, Phys. Med. Biol., 48 (2003), 2509-2525.18. U. Zurbuchen, C. Holmer, K. S. Lehmann, T. Stein, A. Roggan, C. Seifarth, et al., Determination of the temperature-dependent electric conductivity of liver tissue ex vivo and in vivo: Importance for therapy planning for the radiofrequency ablation of liver tumours, Int. J. Hyperth., 26 (2010), 26-33.19. E. G. Macchi, M. Gallati, G. Braschi, E. Persi, Dielectric properties of RF heated ex vivo porcine liver tissue at 480 kHz: measurements and simulations, J. Phys. D Appl. Phys., 47 (2014), 485401.21. E. Ewertowska, R. Quesada, A. Radosevic, A. Andaluz, X. Moll, F. G. Arnas, et al., A clinically oriented computer model for radiofrequency ablation of hepatic tissue with internally cooled wet electrode, Int. J. Hyperth., 35 (2019), 194-204.30. M. Qiu, A. Singh, D. Wang, J. Qu, M. Swihart, H. Zhang, P. N. Prasad, Biocompatible and biodegradable inorganic nanostructures for nanomedicine: Silicon and black phosphorus, Nano Today, 25 (2019), 135-155.33. A. Andreozzi, L. Brunese, M. Iasielllo, C. Tucci, G. P. Vanoli, Modeling heat transfer in tumors: A review of thermal therapies, Ann. Biomed. Eng., 47 (2019), 676-693

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

Measurement and image-based estimation of dielectric properties of biological tissues — past, present, and future —

The dielectric properties of biological tissues are fundamental pararmeters that are essential for electromagnetic modeling of the human body. The primary database of dielectric properties compiled in 1996 on the basis of dielectric measurements at frequencies from 10 Hz to 20 GHz has attracted considerable attention in the research field of human protection from non-ionizing radiation. This review summarizes findings on the dielectric properties of biological tissues at frequencies up to 1 THz since the database was developed. Although the 1996 database covered general (normal) tissues, this review also covers malignant tissues that are of interest in the research field of medical applications. An intercomparison of dielectric properties based on reported data is presented for several tissue types. Dielectric properties derived from image-based estimation techniques developed as a result of recent advances in dielectric measurement are also included. Finally, research essential for future advances in human body modeling is discussed.peer-reviewe

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

Broadband Dielectric Spectroscopy with a Microwave Ablation Antenna

Microwave ablation is a technique used to treat tumorous tissue. Its clinical use has been greatly expanding in the last few years. Because the design of the ablation antenna and the success of the treatment greatly depend on the accurate knowledge of the dielectric properties of the tissue being treated, it is highly valuable to have a microwave ablation antenna that is also able to perform in-situ dielectric spectroscopy. In this work, an open-ended coaxial slot ablation antenna design operating at 5.8 GHz is adopted from previous work, and its sensing abilities and limitations are investigated in respect of the dimensions of the material under test. Numerical simulations were performed to investigate the functionality of the floating sleeve of the antenna and to find the optimal de-embedding model and calibration option for obtaining accurate dielectric properties of the area of interest. Results show that, as in the case of the open-ended coaxial probe, the accuracy of the measurement greatly depends on the likeness between the calibration standards' dielectric properties and the material under test. Finally, the results of this paper clarify to which extent the antenna can be used to measure dielectric properties and paves the way to future improvements and the introduction of this functionality into microwave thermal ablation treatments

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

Thermal modeling of lesion growth with radiofrequency ablation devices

BACKGROUND: Temperature is a frequently used parameter to describe the predicted size of lesions computed by computational models. In many cases, however, temperature correlates poorly with lesion size. Although many studies have been conducted to characterize the relationship between time-temperature exposure of tissue heating to cell damage, to date these relationships have not been employed in a finite element model. METHODS: We present an axisymmetric two-dimensional finite element model that calculates cell damage in tissues and compare lesion sizes using common tissue damage and iso-temperature contour definitions. The model accounts for both temperature-dependent changes in the electrical conductivity of tissue as well as tissue damage-dependent changes in local tissue perfusion. The data is validated using excised porcine liver tissues. RESULTS: The data demonstrate the size of thermal lesions is grossly overestimated when calculated using traditional temperature isocontours of 42°C and 47°C. The computational model results predicted lesion dimensions that were within 5% of the experimental measurements. CONCLUSION: When modeling radiofrequency ablation problems, temperature isotherms may not be representative of actual tissue damage patterns

LARGE TARGET TISSUE NECROSIS OF RADIOFREQUENCY ABLATION USING MATHEMATICAL MODELLING

Radiofrequency ablation (RFA) is a clinic tool for the treatment of various target tissues. However, one of the major limitations with RFA is the ‘small’ size of target tissues that can be effectively ablated. By small it is meant the size of the target tissue is less than 3 cm in diameter of the tissue otherwise ‘large’ size of tissue in this thesis. A typical problem with RFA for large target tissue is the incompleteness of tumour ablation, which is an important reason for tumour recurring. It is widely agreed that two reasons are responsible for the tumour recurring: (1) the tissue charring and (2) the ‘heat-sink’ effect of large blood vessels (i.e. ≥3 mm in diameter). This thesis study was motivated to more quantitatively understand tissue charring during the RFA procedure and to develop solutions to increase the size of target tissues to be ablated. The thesis study mainly performed three tasks: (1) evaluation of the existing devices and protocols to give a clear understanding of the state of arts of RFA devices in clinic, (2) development of an accurate mathematical model for the RFA procedure to enable a more quantitative understanding of the small target tissue size problem, and (3) development of a new protocol based on the existing device to increase the size of target tissues to be ablated based on the knowledge acquired from (1) and (2). In (1), a design theory called axiomatic design theory (ADT) was applied in order to make the evaluation more objective. In (2), a two-compartment finite element model was developed and verified with in vitro experiments, where liver tissue was taken and a custom-made RFA system was employed; after that, three most commonly used internally cooled RFA systems (constant, pulsed, and temperature-controlled) were employed to demonstrate the maximum size of tumour that can be ablated. In (3) a novel feedback temperature-controlled RFA protocol was proposed to overcome the small target tissue size problem, which includes (a) the judicious selection of control areas and target control temperatures and (b) the use of the tissue temperature instead of electrode tip temperature as a feedback for control. The conclusions that can be drawn from this thesis are given as follows: (1) the decoupled design in the current RFA systems can be a critical reason for the incomplete target tissue necrosis (TTN), (2) using both the constant RFA and pulsed RFA, the largest TTN can be achieved at the maximum voltage applied (MVA) without the roll-off occurrence. Furthermore, the largest TTN sizes for both constant RFA and pulsed RFA are all less than 3 cm in diameter, (3) for target tissues of different sizes, the MVA without the roll-off occurrence is different and it decreases with increase of the target tissue size, (4) the largest TTN achieved by using temperature-controlled RFA under the current commercial protocol is still smaller 3 cm in diameter, and (5) the TTN with and over 3 cm in diameter can be obtained by using temperature-controlled RFA under a new protocol developed in this thesis study, in which the temperature of target tissue around the middle part of electrode is controlled at 90 ℃ for a standard ablation time (i.e. 720 s). There are a couple of contributions with this thesis. First, the underlying reason of the incomplete TTN of the current commercially available RFA systems was found, which is their inadequate design (i.e. decoupled design). This will help to give a guideline in RFA device design or improvement in the future. Second, the thesis has mathematically proved the empirical conclusion in clinic that the limit size of target tissue using the current RFA systems is 3 cm in diameter. This has advanced our understanding of the limit of the RFA technology in general. Third, the novel protocol proposed by the thesis is promising to increase the size of TTN with RFA technology by about 30%. The new protocol also reveals a very complex thermal control problem in the context of human tissues, and solving this problem effectively gives implication to similar problems in other thermal-based tumour ablation processes

Nonosecond Pulsed Electric Field Induced Changes in Dielectric Properties of Biological Cells

Nanosecond pulsed electric field induced biological effects have been a focus of research interests since the new millennium. Promising biomedical applications, e.g. tumor treatment and wound healing, are emerging based on this principle. Although the exact mechanisms behind the nanosecond pulse-cell interactions are not completely understood yet, it is generally believed that charging along the cell membranes (including intracellular membranes) and formation of membrane pores trigger subsequent biological responses, and the number and quality of pores are responsible for the cell fate. The immediate charging response of a biological cell to a nanosecond pulsed electric field exposure relies on the dielectric properties of its cellular components. Conversely, intense nanosecond pulses will change these properties due to conformational and functional changes. Hence, an understanding of biodielectric phenomena is necessary to explain the underlying interaction mechanisms between nanosecond pulses and biological materials. To this end, we have investigated the changes in dielectric characteristics of biological cells and tissues after exposure to multiple nanosecond pulses. Significant differences have been observed in dielectric properties and membrane integrity of Jurkat cells for exposures to nanosecond and microsecond pulsed electric fields despite delivery of the same energy, suggesting different pore formation and development mechanisms. The effect of nanosecond pulsed electric fields on the dielectric properties of Jurkat cells is long-lasting which is consistent with predictions of much longer pore resealing times for shorter pulses. Strong correlation between short-term plasma membrane conductivity and long-term cell survival has also been observed for different nanosecond-exposure conditions. Together with the studies on tissues, we demonstrate that dielectric spectroscopy is capable of assessing conformational and possibly functional changes of cells after exposure to nanosecond pulsed electric fields on biologically relevant time scales, and in turn, evaluate and compare the efficacy of chosen pulse parameters

Computational Models and Experimentation for Radiofrequency-based Ablative Techniques

Las técnicas ablativas basadas en energía por radiofrecuencia (RF) se emplean con el fin de lograr un calentamiento seguro y localizado en el tejido biológico. En los últimos años ha habido un rápido crecimiento en el número de nuevos procedimientos médicos que hacen uso de dichas técnicas, lo cual ha ido acompañado de la aparición de nuevos diseños de electrodos y protocolos de aplicación de energía. Sin embargo, existen todavía muchas incógnitas sobre el verdadero comportamiento electro-térmico de los aplicadores de energía, así como de la interacción energía-tejido en aplicaciones concretas. El principal propósito de esta Tesis Doctoral es adquirir un mejor conocimiento de los fenómenos eléctricos y térmicos involucrados en los procesos de calentamiento de tejidos biológicos mediante corrientes de RF. Esto permitirá, por un lado, mejorar la eficacia y seguridad de las técnicas actualmente empleadas en la clínica en campos tan diferentes como la cirugía cardiaca, oncológica o dermatológica; y por otro, sugerir mejoras tecnológicas para el diseño de nuevos aplicadores. La Tesis Doctoral combina dos metodologías ampliamente utilizadas en el campo de la Ingeniería Biomédica, como son el modelado computacional (matemático) y la experimentación (ex vivo e in vivo). En cuanto al área cardiaca, la investigación se ha centrado, por una parte, en mejorar la ablación intraoperatoria de la fibrilación auricular por aproximación epicárdica, es decir, susceptible de ser realizada de forma mínimamente invasiva. Para ello, se ha estudiado mediante modelos matemáticos un sistema de medida de la impedancia epicárdica como método de valoración de la cantidad de grasa previo a la ablación. Por otra parte, se ha estudiado cómo mejorar la ablación de la pared ventricular por aproximación endocárdica-endocárdica (septo interventricular) y endocárdica-epicárdica (pared libre del ventrículo). Con este objetivo, se han comparado mediante modelado por computador la eficacia de los modos de ablación bipolar y unipolar en términos de la transmuralidad de la lesión en la pared ventricular. En lo que respecta al área de cirugía oncológica, la investigación se ha centrado en la resección hepática asistida por RF. Las técnicas de calentamiento por RF deberían ser capaces de minimizar el sangrado intraoperatorio y sellar vasos y ductos mediante la creación de una necrosis coagulativa por calentamiento. Si este calentamiento se produce en las cercanías de grandes vasos, existe un problema potencial de daño a la pared de dicho vaso. En este sentido, se ha evaluado con modelos matemáticos y experimentación in vivo si el efecto del flujo de sangre dentro de un gran vaso es capaz de proteger térmicamente su pared cuando se realiza una resección asistida por RF en sus cercanías. Además, se ha realizado un estudio computacional y experimental ex vivo e in vivo del comportamiento electro-térmico de aplicadores de RF bipolares internamente refrigerados, puesto que representan una opción más segura frente a los monopolares en la medida en que las corrientes de RF fluyen casi exclusivamente por el tejido biológico situado entre ambos electrodos. Respecto al área dermatológica, la investigación se ha centrado en mejorar el tratamiento de enfermedades o desórdenes del tejido subcutáneo (tales como lipomatosis, lipedema, enfermedad de Madelung y celulitis) mediante el estudio teórico de la dosimetría correcta en cada caso. Para ello, se han evaluado los efectos eléctricos, térmicos y termo-elásticos de dos estructuras diferentes de tejido subcutáneo durante el calentamiento por RF, y se ha cuantificado el daño térmico producido en ambas estructuras tras dicho calentamientoGonzález Suárez, A. (2014). Computational Models and Experimentation for Radiofrequency-based Ablative Techniques [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/36502TESI