Master of Science / Department of Electrical and Computer Engineering / Punit Prakash / Thermal therapies employing interstitial microwave applicators for hyperthermia or ablation are in clinical use for treatment of cancer and benign disease in various organs. However, treatment of targets in proximity to critical structures with currently available devices is risky due to unfocused deposition of energy into tissue. For successful treatment, complete thermal coverage of the tumor and margin of surrounding healthy tissue must be achieved, while precluding damage to critical structures. This thesis investigates two approaches to increase precision of microwave thermal therapy. Chapter 2 investigates a novel coaxial antenna design for microwave ablation (MWA) employing a hemi-cylinderical reflector to achieve a directional heating pattern. A proof of concept antenna with an S₁₁ of -29 dB at 2.45 GHz was used in ex vivo experiments to characterize the antennas’ heating pattern with varying input power and geometry of the reflector. Ablation zones up to 20 mm radially were observed in the forward direction, with minimal heating (less than 4 mm) behind the reflector. Chapter 3 investigates the use of magnetic nanoparticles (MNP) of varying size and geometry for enhancing microwave tissue heating. A conventional dipole, operating at 2.45 GHz and radiating 15 W, was inserted into a 20 mm radius sphere of distributed MNPs and heating measurements were taken 5 mm, 10 mm, and 15 mm radially away. A heating rate of 0.08°C/s was observed at 10 mm, an increase of 2-4 times that of the control measurement. These approaches provide strong potential for improving spatial control of tissue heating with interstitial and catheter-based microwave antennas.

The steady flow model is applied to ablatively accelerated spherical targets for inertial confinement fusion. A parameter study is conducted which identifies regions of good hydrodynamic efficiency. In the limit of very large acceleration the model is seen to become planar and can be used to treat some large aspect ratio shells. A model of charged particle beam driven ablation is presented. The ablation resulting from this form of energy deposition can resemble laser driven albation in some cases, but qualitatively different behavior occurs in certain regimes of the beam power and range. Laser energy deposition by inverse bremsstrahlung is also included. A procedure for descaling the dimensionless results of the steady flow model is presented. This allows for comparison of the model with experiments and numerical simulations.

Après un état de l’art sur l’ablation des lésions osseuses, les expérimentations HIFU sur l’os présentées ont montré un échauffement périosté plus étendu avec un tir profond. Les tirs sur le ciment, dont le coefficient α a été mesuré, reproduisent les mêmes courbes thermiques. Une simulation a été réalisée avec 2 valeurs de α (4.7 et 9.9 dB/cm) : l’échauffement est moins important avec α=4.7. La simulation confirme certains résultats de la thermo-IRM : une élévation thermique maximale au niveau du périoste (zone focale) avec le tir superficiel, un échauffement latéral plus marqué avec le tir profond et une tendance à l’inertie thermique. A partir d’une analyse rétrospective des cas traités par imagerie mini-invasive, l’ablation HIFU semble possible pour 50% des ostéomes ostéoïdes et 35.7% des métastases. 35.9% de cas supplémentaires auraient pu être traités par HIFU si une protection des structures sensibles ou une consolidation étaient réalisées. A 1 MHz, l’interférence des aiguilles avec les US n’était visible qu’avec les aiguilles 13G. Si les aiguilles 18 à 22G interfèrent peu avec les US, un écran acoustique pourrait se former à la suite d’injection de liquide. / After a “state of art” on bone lesions ablation techniques, bone experimentations presented showed that deep focalisation allows the best lateral periosteal heating. On cement, from which the coefficient α was measured, the same thermic curves were observed. A simulation was done with two values of α (4.7 et 9.9 dB/cm). A higher heating at the periosteal focal point with superficial focalisation and a higher periosteal lateral heating with deep focalisation with a thermic inertia, were confirmed with simulation. Heating was higher with the high α value. A retrospective analysis of the bone lesions treated with minimally invasive treatment showed that 50% of osteoid osteomas and 35.7% of metastases were classified as suitable with MRgHIFU alone. 35.9% additional cases may have been treated with dissection or consolidation. At 1 MHz, US distortion due to the presence of needles in the US cone was observed only with the 13-gauge needle. However, if 18 to 22G needles may induce few distortion, an acoustic barrier may appear if the liquid injected flows in front of the US.

Ce travail nous a permis de proposer un cadre pour sonder la morphogenèse d'une micro-colonie bidimensionnelle. Plus particulièrement, nous avons exploré la manière dont les effets individuels de croissance et d'adhésion se combinaient au cours de la croissance de la micro-colonie. Nous avons montré (i) que l'adhésion de cellules isolées est asymétrique du fait d'un vieux pôle plus ancré et (ii) que l'allongement des bactéries peut induire des forces de poussée à l'intérieur des colonies. Dans la mesure où ces deux effets, combinés à l'échelle d'une micro-colonie, sont susceptibles de générer des contraintes mécaniques, nous avons développé une technique pour mesurer les forces d'adhésion résultantes à l'aide de substrats déformables. Nous avons ainsi démontré que des adhésions focales sont créées et rompues dynamiquement, avec un biais au vieux pôle des cellules. Nous avons aussi examiné le rôle de l'adhésion sur la forme des colonies. Nous avons montré que l'adhésion polaire était responsable de la transition d'un régime de croissance linéaire à un régime bidimensionnel qui est observée après la première division. Pour des colonies de taille plus importante, le niveau d'adhésion était aussi corrélé avec la forme globale des colonies. Enfin, l'adhésion est aussi impliquée dans la transition d'une colonie bidimensionnelle à une colonie tridimensionnelle. L'ensemble de ces résultats suggère que l'expression des adhésines ainsi que leur localisation à la surface des cellules pourraient permettre aux bactéries de moduler activement la forme du groupe dans lequel elles vivent. / In this work, we propose a framework to understand the morphogenesis of two-dimensional microcolonies. In particular, we have explored how growth and adhesion of individual cells compete during microcolony extension. We have shown (i) that isolated cells display an asymmetry in their adhesion, which is higher at the old pole, (ii) that bacterial elongation can result in pushing forces inside the colony. Since the combination of these two effects is expected to produce mechanical stress at the scale of the microcolony, we have developed a method to measure the resulting adhesion forces using deformable substrates. We have demonstrated that focal adhesions are dynamically established and ruptured, with a bias towards the old poles. We have also probed the role of adhesion in the shape of the colony. We have shown that polar adhesion drives the transition from a linear to a two-dimensional growth after the first division. At larger colony sizes, the level of adhesion continues to correlate with the global shape of the colony. Finally, adhesion is involved in the transition from a two-dimensional to a three-dimensional colony. Taken together, our results suggest that the expression of adhesins and their location at the surface of the cells could be levers by which bacteria actively modulate the shape of the group in which they reside.

Le développement des instabilités hydrodynamiques lors d'une expérience de fusion par confinement inertiel représente un sévère obstacle à l'obtention des conditions nécessaires à l'allumage et l'auto-entretien des réactions thermonucléaires. Il est ainsi crucial de comprendre, modéliser et éventuellement contrôler ces instabilités. L'instabilité se développant au front d'ablation est particulièrement étudiée dans le cadre du schéma d'attaque directe, à cause notamment du phénomène d'empreinte laser. Cependant le stade fortement non-linéaire de l'instabilité de Rayleigh-Taylor au front d'ablation reste peu explore. Cette étude vise donc à analyser ce régime.Dans un premier temps, une nouvelle plateforme expérimentale est développée sur le laser National Ignition Facility (NIF) permettant l'étude de phénomènes hydrodynamiques avec plusieurs dizaines de nanosecondes d'impulsion laser. Cette plateforme est ensuite calibrée avec l'étude de la croissance d'une perturbation 2D sous l'effet de l'instabilité de Rayleigh-Taylor. Une plateforme de simulations numériques 2D est également développée sur le code hydrodynamique CHIC capable de modéliser les expériences réalisées.L'étude du régime fortement non-linéaire de l'instabilité de Rayleigh-Taylor est réalisée a partir d'une perturbation multimode 3D imprimée par laser.L'impact de la condition initiale est étudiée en utilisant un faisceau d'empreinte lisse d'une part et non lisse d'autre part. L'analyse des données de radiographie dans l'espace de Fourier et dans l'espace réel permet d'évaluer tous les différents paramètres de l'instabilité (taux de croissance linéaire, vitesses de saturation, taux de coalescence de bulles et paramètre de croissance auto-semblable ) et de comparer les mesures aux modèles existants.L'importance de la condition initiale au stade fortement non-linéaire de la perturbation est ainsi démontrée dans les résultats obtenus. / Experimental and numerical study of the non-linear stage of the ablative Rayleigh-Taylor instability in direct drive

"One of the general processes of interest in Pulsed Plasma Thrusters is the ablation of the solid fuel. In general, ablation occurs when a short pulse of applied energy removes a portion of the fuel surface. Although this ablation process is relatively straight-forward in simple materials that sublimate, ablation in Pulsed Plasma Thrusters is significantly more complicated. This is caused by the transient conditions and the complex behavior of Teflon that does not sublimate but rather undergoes both physical and chemical changes prior to leaving the surface. These two effects combine to make Teflon ablation a highly nonlinear function of heat flux, material property variations, changing molecular weight, and phase transformation behavior. To gain greater insight into the ablation process, a one-dimensional ablation model is developed that addresses the more detailed thermal and thermodynamic behavior of Teflon during simulated operation of a Pulsed Plasma Thruster. The mathematical model is based on the work of Clark (1971), which focused on two-phase, one-dimensional Teflon ablation in the context of thermal protection systems. The model is modified for use in simulated PPT operations and implemented numerically using an adaptive non-uniform grid, explicit finite-difference techniques, and a volume fraction method to capture the interface between the crystalline and amorphous Teflon phases. The ablation model is validated against analytical heat transfer and ablation solutions and compared with previous experimental results. The Teflon ablation model is used to analyze several general ablation scenarios in addition to specific PPT conditions to gain greater insight into long-duration thruster firing, post-pulse material ablation, variable heat flux effects, variable material property effects, and the impact of surface re-crystallization on particulate emission. These simulations are considered in the context of prior experimental investigations of Pulsed Plasma Thrusters. The results of these simulations demonstrate the success of the numerical ablation model in predicting experimental trend and suggest potential paths of moderately improving thruster efficiency and operational repeatability in the future. "

Les microchip lasers à impulsions sub-nanosecondes peuvent être des alternatives intéressantes aux lasers à impulsions femtosecondes pour le micro-usinage des matériaux transparents par absorption multiphotonique. Ces lasers peuvent facilement atteindre les puissances crêtes nécessaires pour déclencher l'ablation de tous les matériaux, y compris les diamants, céramiques, plastiques, et des verres. En outre, ils sont de faible coût, avec un design compact et robuste. Dans cette thèse, un micro-chip laser Nd:YAG amplifié (532 nm, 300 ps) a été utilisé pour la micro-gravure et le marquage de différents types de matériaux transparents, comme le verre borosilicate D263, le verre BK7 et le thermoplastique SBS. L'analyse des résultats a montré un bon accord avec le modèle d'expulsion de matière suite à la génération d'un plasma provoqué par une absorption laser à deux photons. Une résolution sub-micronique de marquage a été obtenue à l'intérieur d'un verre de borosilicate. Des canaux microfluidiques pour capteurs optiques ont été gravés sur verre BK-7 comprenant des guides d'ondes réalisés par échange d'ionique. Des réseaux denses de micro-canaux ont été fabriqués à la surface de matériaux thermoplastiques avec une zone affectée par les effets thermiques limités à quelques micromètres. En conclusion, ce travail de thèse montre que l'utilisation de ce type de laser permet un micro-usinage de très haute résolution avec des effets thermiques limités. / Microchip lasers with sub-nanosecond pulses are attractive alternative to femtosecond lasers for micromachining in transparent materials by multiphoton absorption. These lasers can easily reach pulse peak powers that are needed to trigger ablation in all materials, including diamond, ceramics, plastics, and glasses. In addition, they are low cost with compact and rugged design. In this thesis, a microchip laser (532 nm, 300 ps) has been used for micro-engraving and marking different types of transparent materials such as borosilicate D263, BK7, and SBS thermoplastic. Experimental resultsare rationalized by the model of matter explosion following the plasma generation induced by the laser two-photon absorption. Sub-micron resolution embedded marking is demonstrated inside borosilicate glass. Micro fluidic channels for optical sensors are engraved on BK-7 glass with ion-doped waveguides. Arrays of dense micro channels are fabricated at the surface of thermoplastics with a zone affected by thermal effects limited to the micron range. In summary, this thesis demonstrates that this type of laser can be efficiently used for high-resolution micro-machining transparent materials with minimal thermal effects.

The objective of this research is to develop automated and integrated microsystems for high-resolution imaging and high-throughput phenotyping / laser ablation of C. elegans. These microsystems take advantage of microfluidic technology for precisely handling animals and computer-aid automation for high-throughput processing. We demonstrated automated and high-throughput imaging / sorting and laser ablation of C. elegans. This thesis work is divided into four parts: development of a microsystem for imaging and sorting, development of a microsystem for laser cell ablation, development of a novel temperature measurement method, and development of pressure measurement method in microchannels. First, a microsystem was developed for high-throughput microscopy at high resolution and sorting. The microfluidic chip integrates novel microfluidic components to trap, position, immobilize, and sort/release animals. To characterize device operation and aid design of the device numerical models were developed. The experimental results demonstrate that the device operates robustly in a completely automatable manner. Additionally, a sophisticated control algorithm developed by Matthew Crane (Dr. Hang Lu¡¯s lab) automates the entire process of image acquisition, analysis, and sorting, which allows the system to operate without human intervention. This microsystem sorted worms based on their fluorescent expression pattern with over 95% accuracy per round at a rate of several hundred worms per hour. Secondly, the technologies developed for the imaging/sorting system were adapted and further improved to develop a microsystem for high-throughput cell laser ablation of C. elegans. The multiplex ablation module combined with the embryo trap module enables robust manipulation of embryos/L1-stage C. elegans. In addition, software for image processing and automation was developed to allow high-throughput cell ablations. This system performed ablation of a large number of animals and demonstrated accurate ablation by showing behavioral defects of the ablated worms in a chemotaxis avoidance assay. Thirdly, to aid future development of the microdevices, a novel in situ method for three-dimensionally resolved temperature measurement in microchannels was developed. This method uses video-microscopy in combination with image analysis software (developed by Jaekyu Cho in Dr. Victor Breedveld¡¯s group) to measure Brownian diffusion of nanoparticles that is correlated to temperature. This method offers superior reproducibility and reduced systematic errors. In addition, we demonstrated that this method can be used to measure spatial temperature variations in three dimensions in situ. Lastly, a method for pressure measurement in microdevices was also developed through collaboration with Hyewon Lee (Dr. Hang Lu¡¯s lab) to aid further device optimization. These micro pressure-sensors are composed of two flow layers with a polydimethylsiloxane (PDMS) membrane in between. The membrane deforms as a function of pressure and its deformation is quantified by a simple image-based method. These sensors offer high-precision pressure measurement in broad sensing ranges. In addition, a pressure transduction scheme combined with imaging-based method enables multiplex pressure measurement for simultaneously detecting pressures in multiple locations in a microsystem. Overall, the technologies developed in this thesis will establish a solid basis for continuous improvement of the microsystems for multi-cellular model organisms. This high-throughput technology will facilitate a broad range of biological and medical research.

Heatshield design and analysis has traditionally been a decoupled process, the designer creates the geometry generally without knowledge about how the design variables affect the thermostructural response or how the system will perform under off nominal conditions. Heatshield thermal and structural response analyses are generally performed as separate tasks where the analysts size their respective components and feedback their results to the designer who is left to interpret them. The analysts are generally unable to provide guidance in terms of how the design variables can be modified to meet geometric constraints and not exceed the thermal or structural design specifications. In general, the thermal response analysis of ablative thermal protection systems has traditionally been performed using a one-dimensional finite difference calculation. The structural analyses are generally one, two, or three-dimensional finite element calculations. In this dissertation, the governing differential equations for ablative thermal response are solved in three-dimensions using the finite element method. Darcy' Law is used to model the flow of pyrolysis gas through the ablative material. The three-dimensional governing differential equations for Darcy flow are solved using the finite element method as well. Additionally, the equations for linear elasticity are solved by the finite element method for the thermal stress using temperatures directly from the thermal response calculations. This dissertation also links the analysis of thermal protection systems to their design. The link to design comes from understanding the variation in the thermostructural response over the range of the design variables. Material property sensitivities are performed and an optimum design is determined based on a deterministic analysis minimizing the design specification of bondline temperature subject to appropriate constraints. A Monte Carlo simulation is performed on the optimum design to determine the probability of exceeding the design specifications. The design methodology is demonstrated on the Orion Crew Exploration Vehicle's compression pad design.

Thèse d'exercice : Médecine. Imagerie médicale-Radiodiagnostic : Paris 12 : 2007. / Titre provenant de l'écran-titre. 60 f. : ill. Bibliogr. f. 58-60.