Irreversible electroporation (IRE) is a local ablation technique that has been shown to be both safe and effective in the treatment of solid tumors. The treatment typically consists of inserting needle electrodes directly into the treatment zone and applying high-voltage pulses with widths on the order of hundreds of microseconds. These pulses permeabilize tissue leading to loss of homeostasis among the cells in the treatment zone. Predicting these treatments is challenging as the electric field (EF) induced through the electrode configuration is heterogeneous and is affected by several adjustable parameters. Computational treatment planning models aim to provide a visualization of the treatment zone, and they rely on two critical pieces of information: the electric field distribution (EFD) within the tissue, and the lethal EF threshold for the target tissue type. This work primarily aims to quantify tissue properties necessary for computing the EFD for any electrode configuration, for both traditional IRE as well as next-generation high-frequency IRE treatments. Also included is the determination of pancreatic tumor lethal EF threshold using collagen tissue mimics. Additionally, this work builds on previous reports of an optimal resistance reached during IRE by examining the changes in patients' immune cell populations following treatment, and proposing a method of optimizing these populations by monitoring real-time current achieved during IRE. / Doctor of Philosophy / We are in dire need of new options in cancer therapy, especially in the treatment of tumors that are unresectable, particularly aggressive, or resistant to drugs. Irreversible electroporation (IRE) is a local tumor treatment that has been shown to safely and effectively destroy tumor tissue while leaving behind important structures like blood vessels. As IRE treatments depend on the electric field (EF) generated within the target tissue, it is difficult for clinicians to predict the amount of tissue that will be treated ahead of time. This work aims to collect and examine the information about tumors and the surrounding healthy tissue that is critical to models that can help visualize the treatment and ensure the tumor is exposed to enough lethal energy. Additionally, a new and improved, high-frequency version of IRE (H-FIRE) is explored in terms of its impact on how tissue behaves during the delivery of these types of pulses. In addition to informing models of these therapies, we also explore strategies that clinicians can employ during treatment in order to know when to stop in order to avoid over-treating the area.

Irreversible electroporation (IRE) is a focal ablation technique that has been shown in recent clinical trials to be effective in treating pancreatic cancer. The technique uses short, high voltage pulses to induce nanoscale pores in the target cell membranes, leading to cell death. Due to its non-thermal mechanism, IRE is particularly well suited for treating a tumor that is unresectable due to its close location to crucial structures such as blood vessels and nerves. Predicting the region of treatment is critical for optimal treatment of the tumor. The only predictive tools clinicians currently rely on for IRE treatment planning are computer tomography (CT), ultrasound (US) imaging, and real-time resistance measurement is used to monitor treatment progress. However, there is currently no method to plan optimal pulse parameters such as voltage, pulse duration, pulse number, and electrode spacing prior to treatment. Computational treatment planning models aim to perform this prediction in 3D, however, the electric field region relies on the electrical response of human tissue during IRE. This work quantifies this response for the first time and implements human tissue properties in a patient-specific, 3D treatment planning model. / Master of Science / Pancreatic cancer results in 40,000 deaths every year in the U.S, making it one of the most challenging diseases to treat. The current treatments for this disease fall short and have failed to significantly extend patient life expectancy. A technique called irreversible electroporation (IRE) has been shown in recent clinical trials to be effective in treating pancreatic cancer. IRE excels at treating tumors that are located near important blood vessels, nerves, and other important structures. However, clinicians do not have a way to visualize the region of treatment before surgery. In the research setting, 3D computational models aim to predict this area, but so far these models have been based on animal tissue, often of the incorrect organ type. This work applies IRE to human tissue samples, quantifies its electrical behavior, and implements that information in a personalized, predictive 3D model.

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<p>Accurate knowledge of the frequency- and temperature-dependent dielectric properties of biological tissues is crucial in the development of ultra-wideband diagnostic and therapeutic technologies such as microwave breast cancer detection and hyperthermia treatments. This work examines the temperature dependence of the dielectric properties of the five tissue phantom-types developed by our group as well as porcine fat, muscle and liver tissues for the frequency range from 3 GHz to 10 GHz and for the temperature range from 5 °C to 45 °C. A systematic and simple measurement procedure is developed to measure the continuous temperature dependence of the dielectric properties of the various phantom and tissue types. The temperature trends of the dielectric properties of the different phantoms and tissues are investigated.</p> <p>Linear temperature coefficients at discrete frequencies are impractical and insufficient in ultra-wideband applications when realistic, non-linear numerical models of the dielectric properties are required. Therefore, a compact one-pole Cole-Cole model is used to model the frequency dependence of the dielectric properties of the measured samples at every temperature point. A second- or third-order polynomial is used to model the temperature dependence of the Cole-Cole parameters. The final model is a one-pole Cole-Cole model whose parameters are polynomial functions of temperature. This model enables the estimation of the relative permittivity and the conductivity of the measured phantom and tissue types at any temperature and frequency.</p> / Master of Applied Science (MASc)

This report is a Bachelor thesis in the field of product development and design. It includes a literature review in the field of pressure ulcers and diabetes as well as a design process. The writer of this report, Hanna Länne Rosenlund, is a Mechanical Engineering student at the School of Engineering at Jönköping University. The focus of the education lies within product development and design. Pressure ulcers are a growing health care problem due to an increase in the mean life expectancy as well as an increase in diabetes in the world population. Patients with artificial limbs are often victims of pressure ulcers due to prolonged pressures from the prosthetic sockets on already sensitive areas of the body. Research in the field of pressure-induced injuries is currently taking place at Jönköping University. Their knowledge in finite element modelling and orthopaedic engineering made the research project, PEOPLE, possible. PEOPLE is a collaboration project between the School of Engineering and the School of Health and Welfare at Jönköping University as well as three company partners. In the project they aim to develop a device that will apply pressure to a lower limb while a MR camera takes scans of the limb. The images are later analysed closely by use of the finite element model, which means that all the different tissue properties will be collected for a computer simulation. In that way the tissues reactions to more extreme forms of pressure can be evaluated. This will contribute to the research in hope of eventually being able to predict whether or not a person might be at risk of developing pressure ulcers. A design of the prototype’s chassis was needed to optimize ease of use for both patient and staff, user options to expand research abilities, and sustainability. The design process includes product decomposition, concept generation, conceptual design, brainstorming, design for assembly, and design for component manufacturing, which generated several concepts. The final concept was decided by use of Pugh’s-matrices. The different concepts and the final concept were created in the computer aided design programme, Solid Works. The work resulted in a highly adjustable two-piece concept with optimized ease of use and sustainability due to the use of a Velcro strap. The prototype will come in two different sizes and will be mountable by a developed screwing system and therefore easy to pack, store and replace. It will also contain a new pressure relief system for a more comfortable patient experience. For further development of chassis of this kind, a replaceable pressure relief system would enhance the comfort when usage of larger limbs. When the device will be available for testing, a patient’s point of view can be taken in to consideration for a more reliable thesis and for further optimization of the comfort. / Detta är ett examensarbete på kandidatnivå inom ämnet produktutveckling och design. I arbetet ingår en litterär överblick och sammanfattning av forskning i ämnet angående trycksår och diabetes, samt en designprocess. Författaren, Hanna Länne Rosenlund studerar Maskinteknik med inriktning Produktutveckling och Design på Jönköpings Tekniska Högskola. Trycksår är ett växande problem inom vården på grund av en ökning i medellivslängden samt en ökning av diabetesdiagnoser hos världens befolkning. Patienter med proteser faller ofta offer för trycksår på grund av extrema och långvariga tryckförhållanden där proteserna är lokaliserade. Ett område som redan är känsligare för tryck. Forskning inom tryckframkallande skador pågår just nu på Jönköping University. Deras kunskap inom finita elements modellering samt ortopedingenjörsteknik har gjort detta forskningsprojekt möjligt. Forskningsprojektet heter PEOPLE och är ett samverkningsprojekt mellan Tekniska Högskolan, Hälsohögskolan samt tre företagspartners. Tillsammans siktar de mot att utveckla en prototyp som ska utsätta en lem för ett konstant tryck medan en MR kamera scannar vävnaden. En finit elements modell av lemmen skapas sedan för närmre granskning av vävnaden hos individen. Vävnadens egenskaper samlas sedan för en simulering då man kan utvärdera hur vävnaden skulle reagera på mer extrema former av tryck. På så sätt kan prototypen bidra till forskningen inom ämnet för att förhoppningsvis kunna förutspå ifall en person är vid risk för att utveckla trycksår eller inte. En omkonstruktion av prototypens chassi har utvecklats för att optimera användarvänligheten för både patient och personal, användarmöjligheten för forskningssyfte, samt för att bättre bidra till en mer hållbar lösning. Designprocessen har inkluderat teorier såsom produktnedbrytning, konceptgenerering, konceptutveckling, brainstorming, design for assembly och design for manufacturing som alla har hjälpt till att generera koncept. Det slutgiltiga konceptet valdes med hjälp av Pugh matriser. Koncepten samt det slutliga konceptet skapades i ett CAD (computer aided design) program, Solid Works. Arbetet resulterade i ett justerbart tvådelat koncept med optimerad användarvänlighet och hållbarhet genom att använda sig av ett kardborreband. Prototypen kommer att finnas i två olika storlekar och vara monterbar genom att det går att skruva bort chassit och på så sätt optimera packning, hantering och förvaring. Det kommer också att innehålla ett nyutvecklat system för att underlätta fördelningen av tryck på motsatt sida från indenteringen. För fortsatt utveckling av chassit hade ett utbytbart system för tryckavledning optimerat produkten ytterligare då komforten hade ökat vid användning på större lemmar. När produkten finns tillgänglig för testning i framtiden kommer en patients syn vara möjlig att ta med och på så sätt förstärka trovärdigheten av arbetet samt bidra till fortsatt strävande för komfort.

L’os est un matériau dont les propriétés évoluent tout au long de la vie en fonction des contraintes environnementales. Aujourd’hui, les modalités d’imagerie permettent aux cliniciens d’évaluer la qualité osseuse chez l’adulte. Malheureusement, ces outils diagnostics ne sont pas adaptés pour l’enfant (nocivité des radiations, anesthésie ou sédation nécessaire), et le développement d’un outil clinique nécessite une bonne connaissance des propriétés du tissu osseux pédiatrique.Peu d’études ont analysé les propriétés du tissu osseux au cours de la croissance. Cette pénurie de données de référence s’explique par la faible quantité d’échantillons disponible pour les essais en laboratoire et par la qualité même de ces échantillons pour la plupart «prélevés» et associés à une pathologie de l’enfant.Les objectifs de ce travail de thèse s’inscrivent dans une logique de compréhension des mécanismes et des propriétés de l’os en croissance. L’intérêt majeur de ce travail est donc d’apporter de nouvelles connaissances sur l’os cortical pédiatrique. Les propriétés mécaniques et tissulaires ont été étudiées via l’utilisation de diverses techniques: la microtomographie, la microradiographie, la FTIRM, la biochimie, la compression, la caractérisation ultrasonore et la nanoindentation. Ce travail a permis de mettre en avant l’évolution de l’os cortical pédiatrique vers un état mature: la structure des fibres de collagène se hiérarchise, le tissu se minéralise. Ces changements dans la structure du tissu osseux lui permettent de se rigidifier. Ces travaux de thèse ont permis de mieux comprendre cette évolution, et vont permettre d’avoir une 1ère base de données sur la fibula infantile. / Bone is a material whose properties change throughout life depending on environmental constraints. Today, imaging modalities allow clinicians to assess bone quality in adults. Unfortunately, these diagnostic tools are not suitable for children (harmful radiation, anesthesia or sedation required). Development of a clinical tool requires a good knowledge of pediatric bone tissue properties.Few studies have analyzed the properties of bone tissue during growth. This lack of reference data is due to the small amount of samples available for laboratory testings and the quality of these samples for the most taken and associated with a child's illness.The aims of this thesis are to understand the growing bone. The major interest of this work is to provide new knowledge on pediatric cortical bone. Mechanical, structural and chemical properties have been studied by the use of various techniques: tomography, microradiography, FTIRM, biochemistry, compression, ultrasonic characterization and nanoindentation.This work allowed to highlight that pediatric cortical bone evolves into a mature state: maturation of collagen cross-links, mineralization of bone tissue. These changes in the structure of the bone allows it to stiffen. This work allows to understand this evolution and will enable to have a first database on child fibula.