Monitoring thermal ablation via microwave tomography. An ex vivo experimental assessment

Thermal ablation treatments are gaining a lot of attention in the clinics thanks to their reduced invasiveness and their capability of treating non-surgical patients. The effectiveness of these treatments and their impact in the hospital's routine would significantly increase if paired with a monitoring technique able to control the evolution of the treated area in real-time. This is particularly relevant in microwave thermal ablation, wherein the capability of treating larger tumors in a shorter time needs proper monitoring. Current diagnostic imaging techniques do not provide effective solutions to this issue for a number of reasons, including economical sustainability and safety. Hence, the development of alternative modalities is of interest. Microwave tomography, which aims at imaging the electromagnetic properties of a target under test, has been recently proposed for this scope, given the significant temperature-dependent changes of the dielectric properties of human tissues induced by thermal ablation. In this paper, the outcomes of the first ex vivo experimental study, performed to assess the expected potentialities of microwave tomography, are presented. The paper describes the validation study dealing with the imaging of the changes occurring in thermal ablation treatments. The experimental test was carried out on two ex vivo bovine liver samples and the reported results show the capability of microwave tomography of imaging the transition between ablated and untreated tissue. Moreover, the discussion section provides some guidelines to follow in order to improve the achievable performances

Quantitative interpretation of UWB radar images for non-invasive tissue temperature estimation during hyperthermia

The knowledge of temperature distribution inside the tissue to be treated is essential for patient safety, workflow and clinical outcomes of thermal therapies. Microwave imaging represents a promising approach for non-invasive tissue temperature monitoring during hyperthermia treatment. In the present paper, a methodology for quantitative non-invasive tissue temperature estimation based on ultra-wideband (UWB) radar imaging in the microwave frequency range is described. The capabilities of the proposed method are demonstrated by experiments with liquid phantoms and three-dimensional (3D) Delay-and-Sum beamforming algorithms. The results of our investigation show that the methodology can be applied for detection and estimation of the temperature induced dielectric properties change

Microwave thermometry with potential application in non-invasive monitoring of hyperthermia

Integration of an adaptive finite element method (AFEM) with a conventional least squares method has been presented. As a 3D full-wave forward solver, CST Microwave Studio has been used to model and extract both electric field distribution in the region of interest (ROI) and S-parameters of a circular array consisting of 16 monopole antennas. The data has then been fed into a differential inversion scheme to get a qualitative indicator of how the temperature distribution evolves over a course of the cooling process of a heated object. Different regularization techniques within the Tikhonov framework are also discussed, and a balancing principle for optimal choice of the regularization parameter was used to improve the image reconstruction quality of every 2D slice of the final image. Targets are successfully imaged via proposed numerical methods

Differential ultra-wideband microwave imaging for medical applications

Elektromagnetische Ultrabreitband-Sensorik und -Bildgebung bieten vielversprechende Perspektiven für verschiedene biomedizinische Anwendungen, da diese Wellen biologisches Gewebe durchdringen können. Dabei stellt der Einsatz von leistungsarmen und nichtionisierenden Mikrowellen eine gesundheitlich unbedenkliche Untersuchungsmethode dar. Eine der Herausforderungen im Bereich der ultrabreitbandigen Mikrowellensensorik ist dabei die Extraktion der diagnostisch relevanten Informationen aus den Messdaten, da aufgrund der komplexen Wellenausbreitung im Gewebe meist rechenaufwändige Methoden notwendig sind. Dieses Problem wird wesentlich vereinfacht, wenn sich die Streueigenschaften des zu untersuchenden Objektes zeitlich ändern. Diese zeitliche Varianz der Streueigenschaften kann mit Hilfe einer Differenzmessung über ein bestimmtes Zeitintervall ausgenutzt werden. Im Rahmen dieser Arbeit wird der differentielle Ansatz mittels Ultrabreitband-Sensorik für zwei medizinische Anwendungsszenarien betrachtet. Die dabei genutzten Messsysteme basieren auf dem M-Sequenzverfahren, welches an der Technischen Universität Ilmenau entwickelt wurde. Die erste Anwendung bezieht sich auf das nicht-invasive Temperaturmonitoring mittels Ultrabreitband-Technologie während einer Hyperthermiebehandlung. Hyperthermie ist eine Wärmetherapie zur Unterstützung onkologischer Behandlungen (z. B. Chemo- oder Strahlentherapie). Während einer solchen Behandlung wird das Tumorgewebe um 4 °C bis 8 °C erhöht. Dabei ist es wichtig, dass die Temperatur die obere Grenze von 45 °C nicht überschreitet. In diesem Zusammenhang bietet das differentielle Ultrabreitband-Monitoring eine vielversprechende Technik zur kontinuierlichen und nicht-invasiven Messung der Temperatur im Körperinneren. Der Ansatz basiert auf den temperaturabhängigen dielektrischen Eigenschaften von biologischem Gewebe. Dabei werden elektromagnetische Wellen mit einer geringen Leistung in das Untersuchungsmedium eingebracht, die sich gemäß den dielektrischen Eigenschaften von Gewebe ausbreiten. Wird eine Zielregion (bspw. Tumor) erwärmt, so ändern sich dessen dielektrische Eigenschaften, was zu einem sich ändernden Streuverhalten der elektromagnetischen Welle führt. Diese Änderungen können mittels Ultrabreitband-Sensorik erfasst werden. Für die Evaluierung der gemessenen Änderungen im Radarsignal ist es notwendig, die temperaturabhängigen dielektrischen Eigenschaften von Gewebe im Mikrowellenfrequenzbereich zu kennen. Aufgrund der wenigen in der Literatur vorhandenen temperaturabhängigen dielektrischen Eigenschaften von Gewebe über einen breiten Mikrowellenfrequenzbereich werden in dieser Arbeit die dielektrischen Eigenschaften für Leber, Muskel, Fett und Blut im Temperaturbereich zwischen 30 °C und 50 °C von 500 MHz bis 7 GHz erfasst. Hierzu wird zunächst ein Messaufbau für die temperaturabhängige dielektrische Spektroskopie von Gewebe, Gewebeersatz und Flüssigkeiten vorgestellt und die wesentlichen Einflussfaktoren auf die Messungen analysiert. Die Messdaten werden mit Hilfe eines temperaturabhängigen Cole-Cole Models modelliert, um die dielektrischen Eigenschaften für beliebige Werte im untersuchten Temperatur- und Frequenzbereich berechnen zu können. In einem weiteren Experiment wird die nicht-invasive Erfassung von Temperaturänderungen mittels Ultrabreitband-Technologie in einem experimentellen Messaufbau nachgewiesen. Die Ergebnisse zeigen, dass eine Temperaturänderung von 1 °C zu Differenzsignalen führt, welche mit der genutzten Ultrabreitband-Sensorik (M-Sequenz) detektierbar sind. Die zweite Anwendung befasst sich mit der kontrastbasierten Mikrowellen-Brustkrebsbildgebung. Aufgrund des physiologisch gegebenen geringen dielektrischen Kontrastes zwischen Drüsen- und Tumorgewebe kann durch den Einsatz von Kontrastmitteln, im Speziellen magnetischen Nanopartikeln, die Zuverlässigkeit einer Diagnose verbessert werden. Der Ansatz beruht darauf, dass funktionalisierte magnetische Nanopartikel in der Lage sind, sich selektiv im Tumorgewebe zu akkumulieren, nachdem diese intravenös verabreicht wurden. Unter der Bedingung, dass sich eine ausreichende Menge der Nanopartikel im Tumor angesammelt hat, können diese durch ein äußeres polarisierendes Magnetfeld moduliert werden. Aufgrund der Modulation ändert sich das Streuverhalten der magnetischen Nanopartikel, was wiederum zu einem sich ändernden Rückstreuverhalten führt. Diese Änderungen können mittels leistungsarmen elektromagnetischen Wellen detektiert werden. In dieser Arbeit wird die Detektierbarkeit und Bildgebung von magnetischen Nanopartikeln mittels Ultrabreitband-Sensorik im Mikrowellenfrequenzbereich in Hinblick auf die Brustkrebsdetektion betrachtet. Dabei werden zunächst verschiedene Einflussfaktoren, wie die Abhängigkeit der Masse der magnetischen Nanopartikel, die Magnetfeldstärke des äußeren Magnetfeldes sowie die Viskosität des Umgebungsmediums, in das die Nanopartikel eingebettet sind, auf die Detektierbarkeit der magnetischen Nanopartikel untersucht. Die Ergebnisse zeigen eine lineare Abhängigkeit zwischen dem gemessenen Radarsignal und der Masse der magnetischen Nanopartikel sowie einen nichtlinearen Zusammenhang zwischen der Antwort der magnetischen Nanopartikel und der Feldstärke des äußeren Magnetfeldes. Darüber hinaus konnten die magnetischen Nanopartikel für alle untersuchten Viskositäten erfolgreich detektiert werden. Basierend auf diesen Voruntersuchungen wird ein realistischer Messaufbau für die kontrastbasierte Brustkrebsbildgebung vorgestellt. Die Evaluierung des Messaufbaus erfolgt mittels Phantommessungen, wobei die verwendeten Phantommaterialien die dielektrischen Eigenschaften von biologischem Gewebe imitieren, um eine möglichst hohe Aussagekraft der Ergebnisse hinsichtlich eines praktischen Messszenarios zu erhalten. Dabei wird die Detektierbarkeit und Bildgebung der magnetischen Nanopartikel in Abhängigkeit der Tumortiefe analysiert. Die Ergebnisse zeigen, dass die magnetischen Nanopartikel erfolgreich detektiert werden können. Dabei hängt im dreidimensionalen Bild die Intensität des Messsignals, hervorgerufen durch die magnetischen Nanopartikel, von deren Position ab. Die Ursachen hierfür sind die pfadabhängige Dämpfung der elektromagnetischen Wellen, die inhomogene Ausleuchtung des Mediums mittels Mikrowellen, da eine gleichmäßige Anordnung der Antennen aufgrund der Magnetpole des Elektromagneten nicht möglich ist, sowie das inhomogene polarisierende Magnetfeld innerhalb des Untersuchungsmediums. In Bezug auf den letzten Aspekt wird das Magnetfeld im Untersuchungsbereich ausgemessen und ein Ansatz präsentiert, mit dem die Inhomogenität des Magnetfeldes kompensiert werden kann. Weiterhin wurden die Störeinflüsse des polarisierenden Magnetfeldes auf das Messsystem untersucht. In diesem Zusammenhang werden zwei verschiedene Modulationsarten (eine Modulation mit den zwei Zuständen AN/AUS und eine periodische Modulation) des äußeren polarisierenden Magnetfeldes analysiert. Es wird gezeigt, dass mit beiden Modulationen die magnetischen Nanopartikel bildgebend dargestellt werden können. Abschließend werden die Ergebnisse in Hinblick auf die Störeinflüsse sowie ein praktisches Anwendungsszenario diskutiert.Electromagnetic ultra-wideband sensing and imaging provide promising perspectives in various biomedical applications as these waves can penetrate biological tissue. The use of low-power and nonionizing electromagnetic waves in the microwave frequency range offers an examination method that is harmless to health. One of the challenges in the field of ultra-wideband microwave sensor technology is the extraction of diagnostically relevant information from the measurement data, since the complex wave propagation in tissue usually requires computationally intensive methods. This problem is simplified when the scattering properties of the object under observation change with time. Such a time variance of the scattering properties can be exploited by means of a differential measurement over a certain time interval. In this work, a differential approach using ultra-wideband sensing is considered for two medical applications. The measurement systems used in this work are based on the M-sequence technology developed at the Technische Universität Ilmenau. The first application relates to noninvasive temperature monitoring using ultra-wideband technology during hyperthermia treatment. Hyperthermia is a thermal therapy to support oncological treatments (e.g. chemotherapy or radiotherapy). During such a treatment, the tumor tissue is heated by 4 °C to 8 °C, whereby it is important that the temperature does not exceed the upper limit of 45 °C. In this context, differential ultra-wideband monitoring offers a promising technique for continuous and noninvasive temperature monitoring inside the body. The approach is based on the temperature-dependent dielectric properties of biological tissue. In this method, low power electromagnetic waves are emitted into the medium under investigation. These waves propagate according to the dielectric properties of tissue. If a target region (e.g. tumor) is heated, its dielectric properties will change, which leads to a changing scattering behavior of the electromagnetic wave. These changes can be detected in the measured reflection signals using ultra-wideband microwave technology. To evaluate the measured changes in the radar signal, it is necessary to know the temperature-dependent dielectric properties of tissue in the microwave frequency range. Due to the lack of knowledge of temperature-dependent dielectric properties of tissues over a wide microwave frequency range, the dielectric properties for liver, muscle, fat and blood in the temperature range between 30 °C and 50 °C from 500 MHz to 7 GHz are acquired in this work. For this purpose, a measurement setup for the temperature-dependent dielectric spectroscopy of tissue, tissue substitutes and fluids is presented. Furthermore, the main influences on measuring the temperature-dependent dielectric properties are analyzed. The measured data are modeled using a temperature-dependent Cole-Cole model in order to calculate the dielectric properties for arbitrary values in the investigated temperature and frequency range. In a further experiment, the noninvasive detection of temperature changes using ultra-wideband microwave technology is demonstrated in an experimental measurement setup. The results show that a temperature change of 1 °C results in differential signals that are detectable by means of ultra-wideband pseudo-noise sensing (M-sequence). The second application is dealing with contrast enhanced microwave breast cancer imaging. Due to the physiologically given low dielectric contrast between glandular and tumor tissue, the use of contrast agents, specifically magnetic nanoparticles, can improve the diagnostic reliability. The approach is based on the assumption that functionalized magnetic nanoparticles are able to selectively accumulate in tumor tissue after intravenous administration. Provided that a sufficient amount of nanoparticles has accumulated in the tumor, they can be modulated by an external polarizing magnetic field. Due to the modulation, the scattering behavior of the magnetic nanoparticles changes, which results a changing backscattering behavior. This change can be detected using low-power electromagnetic waves. In this work, the detectability and imaging of magnetic nanoparticles by means of ultra-wideband pseudo-noise sensing in the microwave frequency range is considered with respect to breast cancer detection. First, various influencing factors on the detectability of the magnetic nanoparticles are investigated, such as the mass of the magnetic nanoparticles, the magnetic field strength of the external polarizing magnetic field and the viscosity of the surrounding medium in which the nanoparticles are embedded. The results reveal a linear dependence between the measured radar signal and the mass of the magnetic nanoparticles as well as a nonlinear relationship between the response signal of the magnetic nanoparticles and the magnetic field intensity of the external magnetic field. Furthermore, the magnetic nanoparticles can be successfully detected in all investigated viscosities of the surrounding medium. Based on these preliminary investigations, a realistic measurement setup for contrast enhanced microwave breast cancer imaging is presented. The evaluation of the measurement setup is performed by phantom measurements, where the used phantom materials mimic the dielectric properties of biological tissue to obtain significance of the results with respect to a practical measurement scenario. In this context, the detectability and imaging of the magnetic nanoparticles are analyzed depending on the tumor position and penetration depth, respectively. The results show that the magnetic nanoparticles can be successfully detected. However, the magnetic poles of the electromagnet limit the space for the transmitting and receiving antennas, resulting in an inhomogeneous microwave illumination of the medium under test, which leads to a location-dependent magnetic nanoparticle response. Furthermore, the intensity of the response signal caused by the magnetic nanoparticles in the three-dimensional image depends on their position due to the path-dependent attenuation and the inhomogeneous magnetic field within the investigated medium. Regarding the last point, the external polarizing magnetic field is measured in the investigation area and an approach to compensate for the inhomogeneity of the magnetic field is presented. In addition, the disturbing influences of the polarizing magnetic field on the measurement setup are analyzed. In this context, two different modulation types (a two-state and a periodic modulation) of the external polarizing magnetic field are investigated. It is shown that both modulations can be used to image the magnetic nanoparticles. Finally, the results are discussed with respect to the spurious effects as well as a practical application scenario

Hyperthermia Treatment Monitoring via Deep Learning Enhanced Microwave Imaging: A Numerical Assessment

Simple Summary Non-invasive temperature monitoring during hyperthermia cancer treatment is of paramount importance. It allows physicians to verify the therapeutic temperature is reached in the treated area. Currently, only superficial or invasive thermometry is performed on a clinical level. Magnetic resonance thermometry has been proposed as a a non-invasive alternative but its applicability is limited. Conversely, microwave imaging based thermometry is a potential low cost candidate for non-invasive temperature monitoring. This works presents a computational study in which the use of deep learning is proposed to face the challenges related to the use of microwave imaging in hyperthermia monitoring. The paper deals with the problem of monitoring temperature during hyperthermia treatments in the whole domain of interest. In particular, a physics-assisted deep learning computational framework is proposed to provide an objective assessment of the temperature in the target tissue to be treated and in the healthy one to be preserved, based on the measurements performed by a microwave imaging device. The proposed concept is assessed in-silico for the case of neck tumors achieving an accuracy above 90%. The paper results show the potential of the proposed approach and support further studies aimed at its experimental validation

Imaging of high-intensity focused ultrasound-induced lesions in soft biological tissue using thermoacoustic tomography

An imaging technology, thermoacoustic tomograpy (TAT), was applied to the visualization of high-intensity focused ultrasound (HIFU)-induced lesions. A single, spherically focused ultrasonic transducer, operating at a central frequency of approximately 4 MHz, was used to generate a HIFU field in fresh porcine muscle.Microwave pulses from a 3-GHz microwave generator were then employed to generate thermoacoustic sources in this tissue sample. The thermoacoustic signals were detected by an unfocused ultrasonic transducer that was scanned around the sample. To emphasize the boundaries between the lesion and its surrounding tissue, a local-tomography-type reconstruction method was applied to reconstruct the TAT images of the lesions. Good contrast was obtained between the lesion and the tissue surrounding it. Gross pathologic photographs of the tissue samples confirmed the TAT images.This work demonstrates that TAT may potentially be used to image HIFU-induced lesions in biological tissues

An adaptive finite element method for solving 3D electromagnetic volume integral equation with applications in microwave thermometry

An adaptive finite element method (AFEM) for the numerical solution of an electromagnetic volume integral equation (VIE) is presented. To solve the model VIE, the problem is formulated as an optimal control problem for minimization of Tikhonov\u27s regularization functional. A posteriori error estimates in the obtained finite element reconstruction and in the underlying Tikhonov\u27s functional are derived. Based on these estimates, adaptive finite element algorithms are formulated and numerically tested on the problem of microwave hyperthermia in cancer treatment. In this problem, the temperature change of a target in the computational domain results in the change of its dielectric properties. Numerical examples of monitoring this change show robust and qualitative three-dimensional reconstructions of the target using the proposed adaptive algorithms

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

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

Passive microwave radiometry in biomedical studies

Passive microwave radiometry (MWR) measures natural emissions in the range 1–10 GHz from proteins, cells, organs and the whole human body. The intensity of intrinsic emission is determined by biochemical and biophysical processes. The nature of this process is still not very well known. Infrared thermography (IRT) can detect emission several microns deep (skin temperature), whereas MWR allows detection of thermal abnormalities down to several centimeters (internal or deep temperature). MWR is noninvasive and inexpensive. It requires neither fluorescent nor radioactive labels, nor ionizing or other radiation. MWR can be used in early drug discovery as well as preclinical and clinical studies