Irreversible electroporation (IRE) is a non-thermal tissue ablation modality in which electrical pulses are used to generate targeted disruption of cellular membranes. Clinically, IRE is administered by inserting one or more needles within or around a region of interest, then applying a series of short, high amplitude pulsed electric fields (PEFs). The treatment effect is dictated by the local field magnitude, which is quite high near the electrodes but dissipates exponentially. When cells are exposed to fields of sufficient strength, nanoscale "pores" form in the membrane, allowing ions and macromolecules to rapidly travel into and out of the cell. If enough pores are generated for a substantial amount of time, cell homeostasis is disrupted beyond recovery and cells eventually die. Due to this unique non-thermal mechanism, IRE generates targeted cell death without injury to extracellular proteins, preserving tissue integrity. Thus, IRE can be used to treat tumors precariously positioned near major vessels, ducts, and nerves. Since its introduction in the late 2000s, IRE has been used successfully to treat thousands of patients with focal, unresectable malignancies of the pancreas, prostate, liver, and kidney. It has also been used to decellularize tissue and is gaining attention as a cardiac ablation technique. Though IRE opened the door to treating previously inoperable tumors, it is not without limitation. One drawback of IRE is that pulse delivery results in intense muscle contractions, which can be painful for patients and causes electrodes to move during treatment. To prevent contractions in the clinic, patients must undergo general anesthesia and temporary pharmacological paralysis. To alleviate these concerns, high-frequency irreversible electroporation (H-FIRE) was introduced. H-FIRE improves upon IRE by substituting the long (~100 µs) monopolar pulses with bursts of short (~1 µs) bipolar pulses. These pulse waveforms substantially reduce the extent of muscle excitation and electrochemical effects. Within a burst, each pulse is separated from its neighboring pulses by a short delay, generally between 1 and 5 µs. Since its introduction, H-FIRE burst waveforms have generally been constructed simply by choosing the duration of constitutive pulses within the burst, with little attention given to this delay. This is quite reasonable, as it has been well documented that pulse duration plays a critical role in determining ablation size. In this dissertation, we explore the role of these latent periods within burst waveforms as well as their interaction with other pulse parameters. Our central hypothesis is that tuning the latent periods will allow for improved ablation size with reduced muscle contractions over traditional waveforms. After gaining a simple understanding of how pulse width and delay interact in vitro, we demonstrate theoretically that careful tuning of the delay within (interphase) and between (interpulse) bipolar pulses in a burst can substantially reduce nerve excitation. We then analyze how pulse duration, polarity, and delays affect the lethality of burst waveforms toward determining the most optimal parameters from a clinical perspective. Knowing that even the most ideal waveform will require slightly increased voltages over what is currently used clinically, we compare the clinical efficacy of two engineered thermal mitigation strategies to determine what probe design modifications will be needed to successfully translate H-FIRE to the clinic while maintaining large, non-thermal ablation volumes. Finally, we translate these findings in two studies. First, we demonstrate that burst waveforms with an improved delay structure allow for enhanced safety and larger ablation volumes in vivo. And finally, we examine the efficacy of H-FIRE in spontaneous canine liver tumors while also comparing the ablative effect of H-FIRE in tumor and non-neoplastic tissue in a veterinary clinical setting. / Doctor of Philosophy / Cancer is soon to become the most common cause of death in the United States. In 2023, approximately 2 million new cases of cancer will be diagnosed, leading to roughly 650 thousand lost lives. Interestingly, about half of newly diagnosed cancers are caught in the early stages before the disease has spread throughout the body. With effective local intervention, these patients could potentially be cured of their malignancy. Surgical removal of the tumor is the gold standard, but it is often not possible due to tumor location, patient comorbidities, or organ health status. In some instances, focal thermal ablation with radiofrequency or microwave energy can be performed when resection is not possible. These treatments entail the delivery of thermal energy through a needle electrode, which causes local tissue damage through coagulation (cooking) of the tissue. However, thermal ablation destroys tissue indiscriminately, meaning that any nearby blood vessels or neural components will also be damaged, which precludes thousands of patients from treatment each year. Irreversible electroporation (IRE) was introduced to overcome these challenges and provide a treatment option for patients diagnosed with otherwise untreatable tumors. IRE uses pulsed electric fields to generate nanoscale pores in cell membranes, which lead to a homeostatic imbalance and cell death. Because IRE is a membrane-based effect, it does not rely on thermal effects to generate cellular injury, which allows it to be administered to tumors that are adjacent to critical tissue structures such as major nerves and vasculature. Though IRE opened the door to treating otherwise inoperable tumors, procedures are technically challenging and require specialized anesthesia protocols. High-frequency irreversible electroporation (H-FIRE) was introduced by our group roughly a decade ago to simplify the procedure through the use of an alternate pulsing strategy. These higher frequency pulses offer several advantages such as limiting muscle contractions and reducing the risk of cardiac interference, both of which were concerns with IRE. However, H-FIRE ablations have been limited in size, and there is limited knowledge regarding the optimal pulsing strategy needed in order to maximize the ratio of therapeutic benefits to undesirable side effects like muscle stimulation and Joule heating. In this dissertation, we sought to understand how different pulse parameters affect these outcomes. Using a combination of computational, benchtop, and in vivo experiments, we comprehensively characterized the behavior of user-tunable pulse parameters and identified optimal methods for constructing H-FIRE protocols. We then translated our findings in a proof-of-principle study to demonstrate the ability of newly introduced waveform designs to increase ablation size with H-FIRE. Overall, this dissertation improves our understanding of how H-FIRE waveform selection affects clinical outcomes, introduces a new strategy for maximizing therapeutic outcomes with minimal side effects, and provides a framework for selecting parameters for specific applications.

Tesis por compendio / [ES] La ablación por radiofrecuencia (RF) se ha convertido en una técnica ablativa importante, ampliamente utilizada en el área de las terapias mínimamente invasivas de la medicina moderna. El avance en el campo de las tecnologías basadas en RF a lo largo de los años ha llevado a un número creciente de aplicaciones en diferentes áreas terapéuticas tales como arritmias cardíacas, epilepsia, oncología, resección asistida, apnea, dolor o cirugía estética. Sin embargo, existe una constante necesidad de desarrollar estudios computacionales y experimentales para mejorar el rendimiento de estas técnicas. El enfoque principal de esta tesis doctoral está centrado en examinar los efectos térmicos y eléctricos de ablación por radiofrecuencia de tejidos para mejorar la eficacia y la seguridad de las terapias y dispositivos basados en energía de radiofrecuencia. Las dos áreas principales de interés han sido el tratamiento del dolor y la cirugía hepática oncológica, que se han organizado en tres estudios independientes. La metodología de los estudios se ha basado en modelos computacionales y estudios experimentales sobre phantom de agar, modelos ex vivo e in vivo y ensayos clínicos. El estudio focalizado en el tratamiento del dolor ha incluido el análisis de los efectos eléctricos y térmicos del tratamiento con radiofrecuencia pulsada (PRF) y el riesgo relacionado con el daño térmico al tejido. Se han estudiado diferentes protocolos pulsados empleados en la práctica clínica utilizando modelos computacionales. La exactitud del modelo se ha validado mediante un modelo en phantom de agar. Se han propuesto también modelos computacionales adicionales para los protocolos pulsados alternativos en los cuales se reduciría el efecto térmico sin afectar al efecto eléctrico. En el estudio se ha discutido también el concepto de electroporación leve como el resultado de PRF. En el área de la cirugía hepática oncológica se han analizado dos técnicas diferentes. El primer estudio se ha centrado en examinar la hidratación del tejido durante la ablación por RF con un nuevo electrodo ICW. El nuevo diseño ha incluido dos agujas de perfusión expandibles integradas en el catéter. El objetivo principal ha sido mejorar la precisión del modelo computacional de ablación por RF de tumor utilizando una geometría realista de la distribución de solución salina en el tejido y evaluar el rendimiento del catéter de RF. Se han modelado diferentes casos de tumor infundido con solución salina y los resultados simulados se han comparado con los datos clínicos de un ensayo en 17 pacientes con cáncer hepático. Con el fin de obtener una distribución espacial realista de la solución salina infundida, se ha empleado un estudio in vivo sobre el modelo de hígado de cerdo. El segundo estudio se ha centrado en el desarrollo de una nueva técnica de sellado endoluminal basada en catéter, como una alternativa más efectiva para el manejo del remanente pancreático. El método ha consistido en una ablación por radiofrecuencia guiada por impedancia con la técnica de pullback. El ajuste del tipo de catéter de RF y del protocolo de ablación se ha realizado mediante modelos porcinos ex vivo. Posteriormente, la efectividad del sellado se ha evaluado sobre un modelo de cerdo in vivo. / [CA] L'ablació per radiofreqüència (RF) s'ha convertit en una tècnica ablativa important, àmpliament utilitzada en l'àrea de les teràpies mínimament invasives de la medicina moderna. L'avanç en el camp de les tecnologies basades en RF al llarg dels anys ha portat a un número creixent d'aplicacions en diferents àrees terapèutiques com ara arítmies cardíaques, epilèpsia, oncologia, resecció assistida, apnea, dolor o cirurgia estètica. No obstant això, hi ha una constant necessitat de desenvolupar estudis computacionals i experimentals per a millorar el rendiment d'aquestes tècniques. Aquesta tesi doctoral ha estat centrada en examinar els efectes tèrmics i elèctrics de l'ablació per radiofreqüència de teixits per tal de millorar l'eficàcia i la seguretat de les teràpies i dispositius basats en energia de radiofreqüència. Dos àrees principals són el tractament del dolor i la cirurgia hepàtica. Aquestos han sigut organitzats en tres estudis independents. La metodologia dels estudis ha estat basada en models computacionals i experimentals sobre phantom d'agar, models ex vivo i in vivo i assajos clínics. L'estudi enfocat en el tractament del dolor ha inclòs l'anàlisi dels efectes elèctrics i tèrmics del tractament amb radiofreqüència polsada (PRF) i el risc relacionat amb el dany tèrmic al teixit. S'han estudiat diferents protocols polsats emprats en la pràctica clínica utilitzant models computacionals. L'exactitud del model ha estat validada per mitjà d'un model de phantom d'agar. S'han proposat també models computacionals addicionals per a protocols polsats alternatius en els quals es reduiria l'efecte tèrmic sense afectar l'efecte elèctric. En aquest estudi s'ha discutit també el concepte d'electroporació lleu com el resultat de PRF. A l'àrea de la cirugía hepàtica han sigut analitzades dos tècniques diferents. El primer estudi s'ha centrat en la hidratació del teixit durant l'ablació per RF amb un nou elèctrode ICW. El nou disseny ha inclòs dos agulles de perfusió expandibles integrades en el catèter. L' objetiu principal ha sigut millorar la precisió del model computacional d' ablació de tumors per RF utilitzant una geometria realista per a la distribució de sèrum salií en el teixit i evaluar el rendiment del catèter de RF. S'han modelat diferents casos de tumor infundit amb sèrum salí i els resultats simulats han sigut comparats amb les dades clíniques d'un assaig dut a terme sobre 17 pacients amb càncer hepàtic. Amb l'objetiu d'obtenir una distribució espacial realista del sèrum salí injectat, s'ha du a terme un estudi in vivo basat en un model de fetge de porc. El segon estudi s'ha centrat en el desenvolupament d'una nova tècnica de tancament endoluminal bassat en catèter, com una alternativa més efectiva per a gestionar el romanent pancreàtic. El mètode ha consistit en una ablació per radiofreqüència guiada per impedància amb la tècnica de pullback. L'ajust del tipus de catèter de RF i del protocol d'ablació ha sigut realitzat per mitjà de models porcins ex vivo. Posteriorment, l'efectivitat del tancament ha sigut avaluada sobre un model de porc in vivo. / [EN] Radiofrequency (RF) ablation has become an important ablative technique widely used in the area of minimally invasive therapies of the modern medicine. The advancement in the field of RF-based technologies over the years has led to a growing number of applications in different therapeutic areas such as cardiac arrhythmias, epilepsy, oncology, assisted resection, apnea, pain or aesthetic surgery. There is, however, a constant need for the development of computer and experimental studies, which would enhance the performance and safety of these techniques. The main focus of this PhD Thesis was on examining the thermal and electrical phenomena behind tissue radiofrequency ablation in order to improve the efficacy and safety of the RF-based therapies and applicators. Two main areas of interest were pain management and oncology, which were organized into three independent studies. The research methodology was based on computer modeling and experimental studies on phantoms, ex vivo and in vivo models, and clinical trials. The research on pain management involved the analysis of electrical and thermal effects of the pulsed radiofrequency (PRF) treatment and the related risk of tissue thermal damage. Different pulse protocols used in clinical practice were studied using computer modeling and the study accuracy was validated by means of agar phantom model. Additional computer models for alternative pulse protocols were also proposed, in which thermal effect would be reduced but the electrical effect would remain unchanged. The study also discussed the concept of a mild electroporation from PRF. In the area of oncology, two different techniques were analyzed. First study focused on examining tissue hydration technique during RF ablation with a novel internally cooled wet (ICW) electrode. The new design involved two expandable perfusion needles built into the catheter. The main aim was to improve the accuracy of computer model of tumor RF ablation using a realistic geometry of saline distribution in tissue, and to assess the performance of the RF catheter. Different cases of saline-infused tumor were modeled and the simulated results were compared with the clinical data from a trial on 17 hepatic cancer patients. An in vivo study on pig liver model was used to obtain a realistic spatial distribution of the infused saline. The second study focused on the development of a new catheter-based endoluminal sealing technique as more effective alternative for management of the pancreatic stump. The method consisted of the impedance-guided radiofrequency ablation with pullback. Fine-tuning involving RF catheter type and ablation protocol was performed using ex vivo porcine models, and posteriorly, sealing effectiveness was assessed on an in vivo pig model. / The completion of this work would have not been possible without the financial support of the Spanish Ministerio de Economía, Industría y Competitividad that provided funding for the development of this research project, my Predoctoral scholarship, and also Travel Grant for the research stay in The Wellman Center for Photomedicine / Ewertowska, E. (2019). Computer modeling and experimentation in radiofrequiency-based minimally invasive therapies [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/134057 / Compendio

Com o aumento dos tratamentos químicos e/ou físicos nos cabelos aos quais são realizados mediante o uso de dispositivos térmicos, há uma maior preocupação a respeito dos danos causados aos cabelos por estes tipos de tratamentos. O conhecimento dos efeitos, benefícios e/ou malefícios, de ingredientes cosméticos em cabelos torna-se necessário, pois facilita a busca por produtos baseada no tipo de cabelo. O principal objetivo do trabalho foi a caracterização físico-química, analítica e térmica de mechas de cabelo de diferentes etnias (caucasiano, oriental e afro-étnico virgem e brasileiro virgem e descolorido) antes e após o uso de ingredientes cosméticos seguido de um tratamento térmico (utilizando piastra) e intercalando com lavagens. O estudo das amostras de cabelo e de uma amostra de queratina animal envolveu a utilização das técnicas de TG/DTG, DSC, análise elementar, FTIR, MEV e técnicas de avaliação de eficácia, como tensão/deformação, penteabilidade e quebra por escovação. A partir da TG/DTG, foi possível avaliar as etapas de decomposição térmica das amostras de cabelo virgem e de queratina animal e estas apresentaram um comportamento térmico semelhante entre si. O estudo cinético não isotérmico por TG mostrou que, dos diferentes tipos de amostras de cabelo virgem, o afro-étnico apresentou menor estabilidade térmica e o oriental foi o mais estável termicamente. Os resultados de DSC corroboraram os obtidos por TG, demonstrando que a amostra de cabelo afro-étnico apresentou temperatura de desnaturação térmica das cadeias de α-queratina menor (TD = 223°C) do que as amostras dos outros tipos de cabelo (TD = 236°C). As mechas de cabelo virgem e clareadas foram tratadas com formulações cosméticas contendo silicones e avaliadas quanto a eficiência destes na proteção térmica dos cabelos. Algumas delas mostraram eficiência na proteção térmica das cadeias de α-queratina, diminuindo o seu grau de desnaturação. Foi possível observar que a associação do calor da piastra com as lavagens sucessivas causou danos tanto à cutícula (conforme resultados de FTIR e MEV), como também, ao córtex dos cabelos (conforme resultados de DSC). Em alguns casos, os danos causados foram tão graves que as camadas mais superficiais da cutícula sofreram descamações. O estudo mostrou, também, que a eficiência da proteção térmica nos cabelos depende do tipo da formulação cosmética em que estes protetores estão incorporados e do estado em que os cabelos se encontram. A DSC permitiu a avaliação da modificação termicamente induzida das cadeias de α-queratina e sua posterior desnaturação. O estudo envolvendo a associação das diferentes técnicas apresentou-se viável na avaliação tanto dos danos causados aos cabelos quanto na eficiência dos ingredientes cosméticos na proteção térmica dos mesmos. / With the increase of chemical and/or physical hair treatments, there is an increased concern about the damage caused by the continued use of thermal equipment. This is due to products identified as \"progressive brush\", widely used by individuals of various types of hair, in order to straighten them that are employed with the mandatory use of piastra. Thus, knowledge about the effects, benefits and/or detriments, of cosmetic ingredients in hair of different ethnic groups becomes necessary because it facilitates the search for products based on the type of hair. The main objective this work was the physicochemical, analytical and thermal characterization of hair samples of different ethnic groups (caucasian, oriental, african-ethnic and brazilian type II) before and after the use of cosmetic ingredients followed by heat treatment, using piastra, interleaved by washes. For such purpose, it was used the TG/DTG, DSC, EA, FTIR, SEM and techniques for evaluation of effectiveness as stress/strain and combing. By TG/DTG, it was possible to evaluate the thermal decomposition events of hair and animal keratin samples and these showed a similar thermal behavior between them. The TG-non isothermal kinetic study showed that, from the different types of virgin hair samples, the african-ethnic hair samples had the lowest thermal stability and oriental hair samples were more thermally stable. The DSC results confirm the results obtained by TG, demonstrating that african-ethnic hair samples had thermal denaturation temperature of α-keratin chains (TD = 223°C) lower than the samples from other types of hair (TD = 236°C). The virgin and bleached hair tresses were treated with cosmetic formulations containing silicones and evaluated the efficiency of the thermal protection of the hair. Some of the formulations tested have shown to be efficient as to its protective effect on the degradation of the α-keratin chains, decreasing the degree of denaturation. It was observed that the combination of the heat of piastra with successive washes caused damage to the hair cuticle (according to the IR and SEM results) as well as the cortex of hair (according DSC results). In some cases, the damage was so severe that the most superficial layers of the cuticle suffered flaking. The study also showed that the efficiency of the thermal protection in the hair depends on the type of cosmetic formulation that these protectors are incorporated and the condition of the hair. DSC technique allowed monitoring of the thermally induced modification of the α-keratin chains and subsequent denaturation. The study of the combination of all the techniques, as presented, is feasible in measuring damage to hair and the efficiency of cosmetic ingredients in protecting them.

Com o aumento dos tratamentos químicos e/ou físicos nos cabelos aos quais são realizados mediante o uso de dispositivos térmicos, há uma maior preocupação a respeito dos danos causados aos cabelos por estes tipos de tratamentos. O conhecimento dos efeitos, benefícios e/ou malefícios, de ingredientes cosméticos em cabelos torna-se necessário, pois facilita a busca por produtos baseada no tipo de cabelo. O principal objetivo do trabalho foi a caracterização físico-química, analítica e térmica de mechas de cabelo de diferentes etnias (caucasiano, oriental e afro-étnico virgem e brasileiro virgem e descolorido) antes e após o uso de ingredientes cosméticos seguido de um tratamento térmico (utilizando piastra) e intercalando com lavagens. O estudo das amostras de cabelo e de uma amostra de queratina animal envolveu a utilização das técnicas de TG/DTG, DSC, análise elementar, FTIR, MEV e técnicas de avaliação de eficácia, como tensão/deformação, penteabilidade e quebra por escovação. A partir da TG/DTG, foi possível avaliar as etapas de decomposição térmica das amostras de cabelo virgem e de queratina animal e estas apresentaram um comportamento térmico semelhante entre si. O estudo cinético não isotérmico por TG mostrou que, dos diferentes tipos de amostras de cabelo virgem, o afro-étnico apresentou menor estabilidade térmica e o oriental foi o mais estável termicamente. Os resultados de DSC corroboraram os obtidos por TG, demonstrando que a amostra de cabelo afro-étnico apresentou temperatura de desnaturação térmica das cadeias de α-queratina menor (TD = 223°C) do que as amostras dos outros tipos de cabelo (TD = 236°C). As mechas de cabelo virgem e clareadas foram tratadas com formulações cosméticas contendo silicones e avaliadas quanto a eficiência destes na proteção térmica dos cabelos. Algumas delas mostraram eficiência na proteção térmica das cadeias de α-queratina, diminuindo o seu grau de desnaturação. Foi possível observar que a associação do calor da piastra com as lavagens sucessivas causou danos tanto à cutícula (conforme resultados de FTIR e MEV), como também, ao córtex dos cabelos (conforme resultados de DSC). Em alguns casos, os danos causados foram tão graves que as camadas mais superficiais da cutícula sofreram descamações. O estudo mostrou, também, que a eficiência da proteção térmica nos cabelos depende do tipo da formulação cosmética em que estes protetores estão incorporados e do estado em que os cabelos se encontram. A DSC permitiu a avaliação da modificação termicamente induzida das cadeias de α-queratina e sua posterior desnaturação. O estudo envolvendo a associação das diferentes técnicas apresentou-se viável na avaliação tanto dos danos causados aos cabelos quanto na eficiência dos ingredientes cosméticos na proteção térmica dos mesmos. / With the increase of chemical and/or physical hair treatments, there is an increased concern about the damage caused by the continued use of thermal equipment. This is due to products identified as \"progressive brush\", widely used by individuals of various types of hair, in order to straighten them that are employed with the mandatory use of piastra. Thus, knowledge about the effects, benefits and/or detriments, of cosmetic ingredients in hair of different ethnic groups becomes necessary because it facilitates the search for products based on the type of hair. The main objective this work was the physicochemical, analytical and thermal characterization of hair samples of different ethnic groups (caucasian, oriental, african-ethnic and brazilian type II) before and after the use of cosmetic ingredients followed by heat treatment, using piastra, interleaved by washes. For such purpose, it was used the TG/DTG, DSC, EA, FTIR, SEM and techniques for evaluation of effectiveness as stress/strain and combing. By TG/DTG, it was possible to evaluate the thermal decomposition events of hair and animal keratin samples and these showed a similar thermal behavior between them. The TG-non isothermal kinetic study showed that, from the different types of virgin hair samples, the african-ethnic hair samples had the lowest thermal stability and oriental hair samples were more thermally stable. The DSC results confirm the results obtained by TG, demonstrating that african-ethnic hair samples had thermal denaturation temperature of α-keratin chains (TD = 223°C) lower than the samples from other types of hair (TD = 236°C). The virgin and bleached hair tresses were treated with cosmetic formulations containing silicones and evaluated the efficiency of the thermal protection of the hair. Some of the formulations tested have shown to be efficient as to its protective effect on the degradation of the α-keratin chains, decreasing the degree of denaturation. It was observed that the combination of the heat of piastra with successive washes caused damage to the hair cuticle (according to the IR and SEM results) as well as the cortex of hair (according DSC results). In some cases, the damage was so severe that the most superficial layers of the cuticle suffered flaking. The study also showed that the efficiency of the thermal protection in the hair depends on the type of cosmetic formulation that these protectors are incorporated and the condition of the hair. DSC technique allowed monitoring of the thermally induced modification of the α-keratin chains and subsequent denaturation. The study of the combination of all the techniques, as presented, is feasible in measuring damage to hair and the efficiency of cosmetic ingredients in protecting them.

Philipp Hoffmann Untersuchung zur Fixierung von Knorpelgewebe mittels laserinduzierter Koagulation Aus der Chirurgischen Tierklinik der Veterinärmedizinische Fakultät der Universität Leipzig, angefertigt im Forschungszentrum für Medizintechnik und Biotechnologie GmbH, Bad Langensalza Eingereicht im Januar 2012 97 Seiten, 59 Abbildungen, 9 Tabellen, 318 Literaturangaben 10 Seiten Anhang Schlüsselwörter: Laser, Löten, Knorpelgewebe, Zugfestigkeit, thermische Schäden Gelenkerkrankungen zählen zu den häufigsten Ursachen von Bewegungseinschränkungen in der Human- und Veterinärmedizin. Neben der konservativen Therapie gibt es zahlreiche chirurgische Therapieansätze, unter denen die verschiedenen Verfahren der autologen Chondrozytenimplantation (ACI) vermehrt in den Fokus gerückt sind. Als unbefriedigend stellt sich aktuell die Fixierung der Implantate bzw. Transplantate dar. Ziel der vorliegenden Arbeit war es, zunächst in vitro, unter Nutzung von Gelenkknorpelgewebe aus Kadavermaterial (Schwein, Rind), ein Verfahren einzuarbeiten, mit dem es möglich ist, durch laserinduzierte Koagulation eines Lötmittels eine Verbindung zwischen zwei Knorpelfragmenten bei einer möglichst geringen Gewebeschädigung herzustellen. Als Lötmittel war ein geeignetes Chromophoren-Protein-Gemisch (CPG) herzustellen, welches so auf die Wellenlänge des zur Verfügung stehenden Lasers angepasst wurde, dass die Herstellung von Lötverbindungen möglich war. Die mechanische Festigkeit der Lötverbindungen wurde in verschiedenen Studien zur Optimierung der Lötmittelzusammensetzung und der Lasereinstellungen durch die Bestimmung der Zugkraft geprüft. Ebenso wurden Untersuchungen zum Auftreten thermischer Schäden am Gewebe durch das lasergestützte Löten vorgenommen. Ausgehend von der Untersuchung der Absorptionseigenschaften verschiedener Chromophore und Proteine wurden verschiedene, auf die Wellenlänge des Lasers (810 nm Diodenlaser) abgestimmte, CPG unter Verwendung des Farbstoffes Indocyaningrün (ICG), welcher in dem in der Humanmedizin zugelassenen Diagnostikum ICG-Pulsion® (PULSION Medical Systems AG, München) enthalten ist, und bovinem Serumalbumin (BSA) hergestellt. Knorpelgewebe absorbiert die Strahlung des Diodenlasers (810 nm) kaum (μa ≈ 0 bis 0,02 cm-1). Das Lötmittel (ICG + BSA), dessen Absorptionsmaximum mit 790 nm nah an der Emissionswellenlänge des Lasers liegt, absorbiert hingegen in diesem Wellenlängenbereich gut. Dadurch kann eine direkte Schädigung des Knorpelgewebes durch die Absorption der Laserstrahlung vermieden werden. In den Studien wurden drei Lötmittel mit unterschiedlichen Anteilen an ICG (1 %, 0,25 % und 0,025 %) bei einem BSA-Gehalt von 60 % verwendet. Die Lötmittel mit 0,025 % und 0,25 % ICG wurden zur Prüfung der Zugfestigkeit der gelöteten Verbindung in Abhängigkeit von der Leistungsdichte und der Expositionszeit untersucht. Das Lötmittel mit 0,025 % ICG wurde in den Untersuchungen zur Abhängigkeit der Zugfestigkeit von der Tierspezies, der Entnahmestelle des Knorpelgewebes und der Lötmitteldicke genutzt. Einflüsse der Lagerung des Lötmittels und der Anzahl an Lötmittelpunkten auf die Zugfestigkeit wurden mit dem Lötmittel mit 0,25 % ICG untersucht. Zusätzlich war zu prüfen ob durch ein Knorpelgewebefragment hindurch das CPG zu koagulieren ist. Zur Untersuchung thermisch bedingter Schäden wurden zum einen Temperaturmessungen an der Oberfläche des Knorpelgewebes, im Bereich des Lötmittels und in verschiedenen Tiefen unterhalb des Lötmittels durchgeführt. Zum anderen erfolgten histologische Untersuchungen der Knorpelgewebeproben nach Laseranwendung. Es ist möglich, mittels laserinduzierter Koagulation eines CPG eine Verbindung von Knorpelgewebe vom Schwein und Rind herzustellen. Mit Steigerung der Leistungsdichte und Verlängerung der Expositionszeit kommt es zur Erhöhung der Zugfestigkeit. Die Zugfestigkeiten waren bei Koagulation des CPG durch das Knorpelfragment hindurch niedriger als die Zugfestigkeiten mit aufgelegtem Lötmittel. Unter Laseranwendung kommt es zu einem steilen Ansteigen der Temperatur im Lötmittel bis zum Erreichen einer Höchsttemperatur. Die Steilheit des Temperaturanstieges und die sich einstellenden Temperaturen nehmen mit Erhöhung des im Lötmittel enthaltenen ICG-Gehaltes und der am Laser eingestellten Leistung zu. Die Temperaturerhöhung ist jedoch weitgehend auf das Lötmittel und dessen Randbereiche begrenzt. Die histologischen Untersuchungen verdeutlichten, dass die Laserbestrahlung von Knorpelgewebe mittels Diodenlaser (810 nm) nur eine sehr geringe Schädigung verursacht. Unter Verwendung eines Lötmittels kommt es durch die vom Lötmittel absorbierte Energie zu Schäden am umliegenden Knorpelgewebe. Diese Schädigung ist auf Randbereiche des Lötmittels begrenzt und nimmt mit steigender Leistung und Expositionszeit zu. Bei einer Leistungsdichte von (5,09 W/cm2) konnte eine Verbindung zwischen zwei Knorpelfragmenten erzielt werden, die bei einer Zugkraft von 13,3 N/cm2 nachgibt und bei der die Schädigungen des Knorpelgewebes minimal sind. Die vorliegenden Untersuchungen haben gezeigt, dass es möglich ist, Knorpelfragmente mittels laserinduzierter Koagulation eines CPGs miteinander zu fixieren. / Philipp Hoffmann Investigation for the fixation of articular cartilage tissue using laser-induced coagulation From the Large Animal Clinic for Surgery, Faculty of Veterinary Medicine, University of Leipzig, prepared at Research Centre of Medical Technology and Biotechnology GmbH, Bad Langensalza Submitted in January 2012 97 Pages, 59 figures, 9 tables, 318 references, 10 pages appendices Keywords: laser, soldering, cartilage tissue, tensile strength, thermal damage Joint diseases are among the most common causes of restricted movement of patients in the human and veterinary medicine. In addition to the conservative therapy, there are numerous surgical therapies, under which the various methods of autologous chondrocyteimplantation, have moved increasingly into the focus of scientific and clinical interest. As problematic and unsatisfactory is currently the fixation of the implants. The aim of this study was, first in vitro, taking advantage of articular cartilage tissue from cadaver material (pig, cattle) to incorporate a process by which it is possible to produce by laser-induced coagulation of solder a connection between two cartilage fragments with the smallest possible tissue damage. As solder was a suitable chromophore-protein-mixture (CPG) to establish which it was adapted to the wavelength of the laser is available, that the production of solder joints was possible. The mechanical strength of solder joints has been examined in several studies to optimize the laser settings and the solder ingredients by determining the tensile strength. Likewise, studies on the occurrence of thermal damage to the tissues were made by the laser-assisted soldering. Based on the study of the absorption properties of various chromophores and proteins the wavelength of the laser (810 nm diode laser) was tuned, and different CPG using the dye indocyanine green (ICG), which is within the acceptable in human medicine ICG-Pulsion ® (Pulsion Medical Systems AG, Munich) is included, and bovine serum albumin (BSA) were prepared. Articular cartilage tissue absorbs the radiation of the diode laser (810 nm) hardly (uA ≈ 0 to 0.02 cm–1). The solder (ICG + BSA), whose absorption maximum at 790 nm is close to the emission wavelength of the laser is absorbed. This can be avoided direct damage to the cartilage tissue through the absorption of laser radiation. In the studies, three solders were used with different proportions of ICG (1 %, 0.25 % and 0.025 %) at a content of 60 % BSA. The solder with 0.025 % and 0.25 % ICG were studied to test the tensile strength of the soldered connection as a function of power density and exposure time. The solder containing 0.025 % ICG was used in the investigations of the dependence of tensile strength of the animal species, the donor site of the cartilage and the solder thickness. Influences of storage the solder and the number of solder dots on the tensile strength were investigated with the solder with 0.25 % ICG. In addition it was to examine if it is possible to coagulate the CPG through an articular cartilage fragment. To investigate thermally induced damage to temperature measurements were performed on the surface of the cartilage tissue in the area of the solder and at various depths below the solder. Secondly, histological examinations were made of the articular cartilage after laser application. It is possible to produce by laser-induced coagulation of a CPG an articular cartilage bonding of pig and cattle. With increasing power density and lengthening the exposure time leads to the increase in tensile strength. The tensile strengths were measured with coagulation of the CPG passed through the cartilage fragment is lower than the tensile strengths with applied solder. Under laser application leads to a steep rise in temperature in the solder to reach a maximum temperature. The rate of temperature rise increases with increasing the solder contained in ICG content and on the laser power set. The temperature rise is limited largely to the solder and its peripheral areas. The histological examinations showed that the laser irradiation of cartilage tissue using diode laser (810 nm) only a very little damage caused. Using a solder it comes through the energy absorbed by the solder and damage to the surrounding articular cartilage tissue. This damage is limited to border areas and the flux increases with increasing power and exposure time. At a power density of (5.09 W/cm2) was a connection between two cartilage fragments are obtained, which yields at a tensile force of 13.3 N/cm2 and where the damage to the cartilage tissue is minimal. The present studies have shown that it is possible cartilage fragments by laser-inducedcoagulation of a CPG to fix each other.

Cette thèse s’inscrit dans le contexte des contrôles non destructifs du béton par ultrasons. Nous focalisons notre étude sur les mesures en acoustique non linéaire qui permettent d’ausculter le béton à l’échelle mésoscopique où les ondes interagissent avec les microfissures et le réseau de porosité. Les paramètres associés sont connus comme étant beaucoup plus sensibles que ceux issus des mesures linéaires. Le béton est un matériau hétérogène et complexe, ce qui présente un comportement fortement non linéaire croissant avec l’état endommagé.Nous développons dans cette thèse un type de mesure non linéaire : Dynamic Acousto-Elastic Testing (DAET). Cette technique fondée sur le principe d’une excitation dynamique du matériau, utilise les ondes ultrasonores pour suivre la variation du comportement élastique en fonction de l’amplitude d’excitation. Nous focalisons notre étude sur le problème du béton d’enrobage qui tient un rôle essentiel dans la durée de vie d’une structure de génie civil. Nous étudions l’interaction des mesures non linéaires par DAET avec les ondes de Rayleigh qui se propagent dans le béton d’enrobage. Nous montrons la sensibilité importante de l’évolution de paramètres non linéaires en fonction de l’endommagement thermique et de la carbonatation.Par la suite, nous proposons une nouvelle méthodologie de la mesure DAET, dans laquelle la vibration transitoire est générée par un impact et les ondes sont générées en continue. Nous présentons différentes applications de la méthode proposée, incluant le cas des éprouvettes de grandes dimensions. Cette approche ouvre de larges possibilités de transposer les mesures pour une application sur site. / This thesis is related to the field of nondestructive evaluation of concrete by ultrasound. We focus our study on nonlinear acoustic-based measurements that allow the concrete auscultation at mesoscopic scale where waves interact with microcracks and porosity network. The nonlinear parameters are known to be much more sensitive than those from linear measurements. Concrete is a heterogeneous and complex material. Its behavior is highly nonlinear with increasing damaged state.We develop in this thesis a type of nonlinear measurement: Dynamic Acousto-Elastic Testing (DAET). This technique is based on the principle of a dynamic excitation of the material, using ultrasounds to follow the variation of the elastic behavior depending on the excitation amplitude. We focus our study on the problem of concrete cover which holds a key role in the life of a civil engineering structure. We study the interaction of the DAET measurement with the Rayleigh waves which propagate in the concrete cover. We show the high sensitivity evolution of non-linear parameters in function of thermal damage and carbonation.Subsequently, we propose a new methodology of DAET measurement, in which the transient vibration is generated by an impact and ultrasounds are generated continuously. We present different applications of the proposed method including the case of large specimens. This approach opens broad possibilities of transposing measurements for on-site application.

Ces dernières années, les modes de Lamb à vitesse de groupe nulle (ZGV) se sont révélés être un outil efficace pour sonder localement et précisément l'épaisseur d'un échantillon ou les propriétés mécaniques de matériaux isotropes ou anisotropes. Ce type particulier d'ondes guidées, telles de fortes résonances locales de la structure, résulte de l'interférence de deux ondes de Lamb ayant une vitesse de phase opposée et coexistant pour un couple fréquence-nombre d'ondes particulier. Les ultrasons laser ont démontré leur capacité à générer et détecter efficacement de telles résonances locales dans la gamme des MHz. En effet, la configuration tout optique, constituée d'une source laser pulsée pour générer les ondes élastiques et d'un interféromètre pour sonder le déplacement normal associé, évite tout contact avec l'échantillon, limitant ainsi l'élargissement ou la suppression de résonances. L'utilisation de modes ZGV pour suivre la fatigue des matériaux et sonder des phénomènes non linéaires reste cependant un défi et constitue le cœur des travaux de recherche présentés ici. La partie théorique porte sur la compréhension de l’effet de la fatigue mécanique sur les modes ZGV à travers l’analyse fréquence-nombre d’ondes des modes de Lamb. La partie expérimentale est consacrée à l’application de cette technique pour l'ECND et le suivi de la fatigue de plaques métalliques minces. Les modes ZGV en ultrasons laser montrent un grand potentiel pour localiser les dommages dus à la fatigue, prédire la vie en fatigue et évaluer qualitativement, voire quantitativement, les différents stades de dommages causés par la fatigue. / In recent years, zero-group-velocity (ZGV) Lamb modes have proven to be an efficient tool to probe locally and very accurately the thickness of a sample or the mechanical properties of either isotropic or anisotropic materials. This particular type of guided waves, corresponding to sharp local resonances of the structure, results of the interference of two Lamb waves having opposite phase velocity and coexisting at a couple given frequency-wavenumber. The laser ultrasonic technique has demonstrated its ability to efficiently generate and detect such local resonances within the MHz frequency range. Indeed, the all-optical setup, consisting of a pulsed laser source to generate elastic waves and of an interferometer to probe the associated normal displacement, avoids any contact with the sample, hence limiting the broadening or suppression of the resonances. Yet, the use of ZGV Lamb modes to monitor material fatigue and to probe nonlinear phenomena remains challenging and is the core of the here-reported research. The theoretical part of this PhD research deals with the understanding of the effect of mechanical fatigue on ZGV Lamb modes through the frequency-wavenumber analyzes of the Lamb waves. The experimental part of the PhD research is dedicated to the application of this technique for the nondestructive characterization and for the monitoring of mechanical and thermal fatigue of thin metal plates. Zero-group-velocity Lamb modes in laser ultrasonics shows great promises to locate fatigue damage, to predict the fatigue lifetime, and to qualitatively, and even quantitatively, assess the different stages of fatigue damage in   m- to potentially cm-thick solid plates.

[pt] A previsão do comportamento de materiais quase-frágeis desde o início de sua degradação até o aparecimento de fraturas pode ser apoiada pelo o uso da mecânica do dano contínuo. Efeitos térmicos, além de mecânicos, podem apresentar contribuição significativa na resposta do material e da estrutura. Nesse sentido, o acoplamento entre os distintos ramos da física descrevem a livre conversão da energia em suas diversas formas. O presente trabalho trata do acoplamento térmico em problemas de dano em materiais quase frágeis, em que são abordados o modelo de dano isótropico e os critério de danificação, bem como leis de evolução do dano térmico e mecânico. Além disso, aspectos inerentes à termodinâmica e transferência de calor são explicitados. O efeito térmico na análise estrutural inicia-se com uma investigação sobre os requisitos para que variações de temperatura produzam tensões térmicas e prossegue com um estudo do efeito no material, que reduz as propriedades de módulo de elasticidade, resistência à tração e à compressão além da energia de fratura. No entanto, a modelagem em elementos finitos da degradação da rigidez da estrutura devido ao processo de dano apresenta problemas de dependência da malha, que requerem o uso de técnicas de regularização da solução. Esse tópico é também abordado no trabalho. Exemplos numéricos demonstram os efeitos do acoplamento termomecânico na previsão da integridade de estruturas de materias quase-frágeis. / [en] Predicting the behavior of almost brittle materials in face of material degradation up to fracture is a topic that can be addressed with the use of continuous damage mechanics. Thermal effects, in addition to mechanical ones, may contribute significantly to the structural and material response. In this sense, the coupling between the different branches of physics takes into account the free conversion of energy in its various forms. The present work is about the thermal-mechanical coupling in in quasi-brittle materials, in which the isotropic damage model and the damage criteria are addressed, as well as the laws of evolution of thermal and mechanical damage. In addition, aspects inherent to thermodynamics and heat transfer are explained. The thermal effect in the structural analysis begins with an investigation of the requirements for temperature variations to produce thermal stresses and follows with a study of the effect of temperature on the material, which affects the elasticity module, the tensile and compression strength, in addition to the fracture energy. However, finite element modeling of stiffness degradation due to the damage process leads to problems of dependence on the mesh, which requires the use of regularization techniques, as addressed in this work. Numerical examples demonstrate the effects of thermo-mechanical coupling in the assessment of structure integrity.

Aerospace research for next-generation travel increasingly focuses on the use of advanced composites to reduce weight and cost while retaining strength. One subset of materials with great potential is based on the combination of resin matrix and glass-fiber reinforcement. This research explores the application of a candidate nanopaper coating with a given composite. Prior research applied a set of given heat fluxes to the top surface of the composite for a set of given periods of time, and subsequently performed a 3-point flexural test to determine the elastic modulus for both the coated and uncoated composite for all of the combinations of heat flux and time. A finite element (FE) model is developed using the ANSYS general purpose finite element analysis (FEA) software that models the degradation in strength/stiffness properties based on heating condition and with the goal of predicting cracking using the element death feature in ANSYS. This thesis describes the prior research suggesting both the need for and novelty of this model, and the procedures used to form the model. The loading conditions of the 3-point flexural test are replicated, and four measures of accuracy are developed based on the force versus displacement curve of the test and the FE model. It is envisioned that continuum-level models developed as a part of these research be applied for design of next-generation space components These measurements are used to verify the FE model, and this model is then employed to extrapolate beyond the context of experimental conditions.

Tesis por compendio / [ES] Esta investigación se centra en la caliza de Prada, una formación del Cretácico inferior ubicada en la zona sur pirenaica de Cataluña (España). Se tomaron muestras de roca de sondeos perforados durante la etapa de diseño del túnel de Tres Ponts. El trabajo aquí presentado explora diferentes aspectos relacionados con el comportamiento térmi-co de la caliza de Prada y las consecuencias derivadas en el túnel de Tres Ponts. En primer lugar, este trabajo describe la variación en las propiedades texturales, físicas y mecánicas de la caliza de Prada después de ser sometida a temperaturas de entre 105 y 600 ºC, y luego enfriada a un ritmo lento o mediante templado, y determina las tem-peraturas clave y los métodos de enfriamiento que afectan más la estabilidad en caso de incendio en el túnel de Tres Ponts. En segundo lugar, esta investigación se centra en las causas y mecanismos implicados en el comportamiento explosivo y la liberación de gas sulfuroso observado en una fracción gris oscuro de muestras de caliza de Prada. Las implicaciones de tales muestras de color gris oscuro son críticas en infraestructuras subterráneas y en minería, ya que el potencial explosivo de esas muestras conlleva el riesgo de fracturación masiva y de disminución brusca en la resistencia. Además, el gas sulfuroso liberado tiene efectos nocivos sobre la salud de las personas y el poten-cial de formar compuestos ácidos que corroen los materiales, acortando su durabilidad y aumentando los costes de mantenimiento. Posteriormente, este trabajo determina si el tratamiento térmico sobre la caliza de Prada tiene un efecto significativo en facilitar su perforabilidad. Comprender la variación en el rendimiento de perforación de la caliza de Prada tratada térmicamente ayudaría a mejorar la eficiencia de los medios mecánicos de excavación. Finalmente, se proponen algunas correlaciones para deter-minar indirectamente las características de resistencia, deformación y perforabilidad de la caliza de Prada tras ser tratada térmicamente, a partir de pruebas simples, rápidas y no destructivas. / [CA] Aquesta investigació es centra en la calcària de Prada, una formació del Cretaci inferior situada a la zona sud pirinenca de Catalunya (Espanya). Es van prendre mostres de roca de sondejos perforats durant l'etapa de disseny del túnel de Tres Ponts. El treball aquí presentat explora diferents aspectes relacionats amb el comportament tèrmic de la calcària de Prada i les conseqüències derivades al túnel de Tres Ponts. En primer lloc, aquest treball descriu la variació en les propietats texturals, físiques i mecàniques de la calcària de Prada després de ser tractada a temperatures d'entre 105 i 600 ºC, i després refredada a un ritme lent o ràpid, i determina les temperatures clau i els mètodes de refredament que afecten més l'estabilitat en cas d'incendi al túnel de Tres Ponts. En segon lloc, aquesta investigació es centra en les causes i mecanismes implicats en el comportament explosiu i l'alliberament de gas sulfurós observat en una fracció gris fosc de mostres de calcària de Prada. Les implicacions de tals mostres de color gris fosc són crítiques en infraestructures subterrànies i en mineria, ja que el potencial explosiu d'aquestes mostres comporta el risc de fracturació massiva i de disminució brusca en la resistència. A més, el gas sulfurós alliberat té efectes nocius sobre la salut de les persones i el potencial de formar compostos àcids que corroeixen els materials, retallant la seua durabilitat i augmentant els costos de manteniment. Posteriorment, aquest treball determina si el tractament tèrmic sobre la calcària de Prada té un efecte significatiu en facilitar la seua perforabilitat. Comprendre la variació en el rendiment de perforació de la calcària de Prada tractada tèrmicament ajudaria a millorar l'eficièn-cia dels mitjans mecànics d'excavació. Finalment, es proposen algunes correlacions per determinar indirectament les característiques de resistència, deformació i perforabilitat de la calcària de Prada després de ser tractada tèrmicament, a partir de proves simples, ràpides i no destructives. / [EN] This research is focused on Prada limestone, a lower Cretaceous formation located in the Catalan south Pyrenean zone (Spain). Rock samples were taken from boreholes drilled during the design stage of the Tres Ponts Tunnel. The work presented here explores different aspects related to the thermal behaviour of Prada limestone and the derived consequences on the Tres Ponts Tunnel. Firstly, this work reports the variation in the textural, physical, and mechanical properties of Prada limestone after being heated at temperatures of between 105 and 600 ºC and then cooled at a slow rate or by quenching and determines key temperatures and cooling methods that would most affect stability in case of a fire in the Tres Ponts Tunnel. Secondly, this research fo-cuses on the causes and mechanisms involved in the explosive behaviour and release of sulphurous gas observed on a dark grey fraction of samples from Prada limestone. Implications of such dark grey samples are critical in underground infrastructure and mining engineering works, as the explosive potential of that sample represents risk of mass fracturing and dramatic strength decay. Moreover, the sulphurous gas released has harmful health effects and may form acid compounds that corrode materials, shorten their durability, and increase maintenance costs. Later, this work determines if thermal treatment on Prada limestone has a significant effect on improving its drilla-bility. Understanding the variation in the drilling performance of the thermally treated Prada limestone would help improve the efficiency of mechanical excavation means. Finally, some correlations are proposed to indirectly determine the strength, deformational, and drillability features of Prada limestone after being thermally treated from simple, quick and non-destructive tests. / This research was partially supported by the Spanish Government [grant number RTI2018-099052-B-I00], also the Vice-Rectorate of Research and Knowledge Transfer at the University of Alicante through projects UAUSTI19-25 and UAUSTI20-20, and by the Departamento de Ingeniería del Terreno at the Universitat Politècnica de València. / Martínez Ibáñez, V. (2021). Effects of high temperatures in the physical, mechanical, and drilling features of Prada limestone [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/171023 / Compendio