L’IRM est de plus en plus utilisée pour diagnostiquer et évaluer un très grand nombre de pathologies. Cette technique présente cependant deux inconvénients majeurs. En effet, les examens restent encore très longs (notamment en imagerie 3D) et la quantification est très difficile par rapport à d’autres modalités comme la tomographie par émission de positons. L’objectif de ce travail de thèse a été de diminuer significativement les temps d’acquisition nécessaires pour l’imagerie volumique et de développer des techniques quantitatives robustes, permettant d’effectuer des suivis longitudinaux.Pour cela, des méthodes innovantes ont été développées à très haut champ magnétique (7T) et validées sur des modèles murins sains et pathologiques. Trois développements majeurs sont ressortis de cette thèse. Tout d’abord, une mesure rapide des temps de relaxation longitudinale (T1) a été développée.Cette méthode basée sur une approche Look-Locker a été couplée avec un échantillonnage en empilement de spirales et a permis d’obtenir au niveau cardiaque des cartes T1 en 3D sur des souris saines et des modèles d’infarctus du myocarde en moins de 15 minutes. Ensuite, une approche dite« spiral-in » a été couplée avec une méthode de multi-échos de spin afin d’accélérer la mesure des temps de relaxation transversale (T2). Cette méthode a permis d’obtenir des cartes T2 en 3D sur des cerveaux de souris saines et métastatiques en moins de 20 minutes. Enfin, une approche hybride couplant les avantages de l’acquisition spiralée et ceux de l’échantillonnage radial a été développée.Cette méthode a été couplée avec une technique de Golden-Angle pour échantillonner aléatoirement l’espace de Fourier et a permis pour la première fois de visualiser une angiographie 3D d’un foie de souris en respiration libre en moins de 12 minutes. Toutes les méthodes développées dans ce travail ont été validées au niveau de leur robustesse et démontrent que l’IRM peut être une technique à la fois rapide et quantitative. Ces développements pourront être transférés vers la clinique dans de futurs travaux. / MRI is more and more used to diagnose and assess a wide range of pathologies. However, this technique is still limited by two disadvantages. Indeed, the acquisition times are too long(especially in 3D) and the quantification is still difficult compared to other techniques like positron emission tomography. The aim of this PhD project was to significantly reduce acquisition times required for 3D imaging and to develop robust quantitative techniques allowing longitudinal studies.To these ends, innovative methods have been developed at very high magnetic field (7T) and validated on healthy and diseased mouse models. Three major developments arose from this work. Firstly, a fast measurement of the longitudinal relaxation time (T1) has been developed. This method based on a Look-Locker approach was coupled with a sampling using stack-of-spirals and allowed to get T1 mapsin 3D in healthy and myocardial infarction models in less than 15 minutes. Then, a "spiral-in" approach was coupled with a multi spin echoes acquisition to accelerate the measurement of the transverse relaxation time (T2). This method allowed to get T2 maps in 3D of healthy and metastatic mouse brains in less than 20 minutes. Finally, a hybrid approach combining the advantages of the spiral acquisition with those of the radial sampling has been developed. This method has been coupled with a Golden-Angle technique for randomly sampling the k-space and allowed for the first time to display a 3Dangiography of a mouse liver in free breathing in less than 12 minutes. All the protocols developed inthis PhD project were validated in terms of robustness and showed that MRI can be a technique both rapid and quantitative. These developments will be transferred to the clinic in future works.

In this thesis, three different types of polymer-based gels are fabricated and characterized for passive and active applications. Silica aerogel is a 3D mesoporous solid material that can be used for thermal insulation or in the biomedical industry. In this thesis, silica aerogel is cross- linked with diisocyanate to improve its strength and flexibility, which greatly opens up the range of applications. Then, soft polymer gel with tissue equivalent characteristics is fabricated to mimic the spin-lattice (T1) and spin-spin (T2) relaxation times for the magnetic resonance imaging (MRI) phantom of a liver with lesions. This study demonstrates a relationship between the composition of a gelling agent, and T1 and T2 modifiers on its dielectric, mechanical and imaging properties. Finally, an ionic electroactive polymer (EAP) that can be actuated on an electric field is fabricated, and its swelling and bending behaviours on design parameters are closely examined.

In this thesis, three different types of polymer-based gels are fabricated and characterized for passive and active applications. Silica aerogel is a 3D mesoporous solid material that can be used for thermal insulation or in the biomedical industry. In this thesis, silica aerogel is cross- linked with diisocyanate to improve its strength and flexibility, which greatly opens up the range of applications. Then, soft polymer gel with tissue equivalent characteristics is fabricated to mimic the spin-lattice (T1) and spin-spin (T2) relaxation times for the magnetic resonance imaging (MRI) phantom of a liver with lesions. This study demonstrates a relationship between the composition of a gelling agent, and T1 and T2 modifiers on its dielectric, mechanical and imaging properties. Finally, an ionic electroactive polymer (EAP) that can be actuated on an electric field is fabricated, and its swelling and bending behaviours on design parameters are closely examined.

This project revolves around the measurement of T1 and T2 relaxation times in the ratbrain, in a multi-center way. That is to say, elaborate an efficient protocol to calculate highresolution 3D map of the brain. This protocol should be applied in different centers andreturn similar results. Finally, procedures should be defined to ease the collaborationbetween the different centers. The first step consisted in in vitro experiments, in whichdifferent sequences were tested. It resulted that the MDEFT sequence with inversionpreparation (MPRAGE) gives the best results in the shortest time for T1. For T2, theMSME sequence was chosen. The next step moved on in vivo experiments on three rats inorder to get used to manipulating living animals and make new adjustments. As thephysiology is not the same on in vitro and in vivo experiments, some parameters had to beslightly adapted. Once the final 2h-protocol was established, it was tested on a populationof ten rats. Experiments were made at the GIN and CRMBM. Different fitting pipelineswere tried (GIN, CRMBM, MIRCEN). The brain was segmented into different regions. Itresulted that the GIN and CRMBM pipelines return the same T1 values using the differentdatasets. The MIRCEN pipeline under-estimates by 200 ms. The three pipelines return similar T2 values. The GIN and CRMBM datasets provide comparable T1 values, but theGIN center presents slightly higher T2 values. Regarding the multi-center collaboration,the different pipelines were ported to the VIP platform so that the scientific community caneasily reuse them.

Η κλασική Απεικόνιση του Μαγνητικού Συντονισμού (ΑΜΣ) βασίζεται στο φαινόμενο του πυρηνικού μαγνητικού συντονισμού όπου η κάθε λέξη ξεχωριστά μας βοηθάει να κατανοήσουμε ποια είναι η προέλευση αυτού του φαινομένου. Συγκεκριμένα, το μετρούμενο σήμα προέρχεται από τους πυρήνες των ατόμων της ύλης, η αλληλεπίδραση μεταξύ των οποίων είναι μαγνητική και το τελικό σήμα εκφρασμένο σε μορφή φασμάτων ή εικόνων λαμβάνεται χρησιμοποιώντας το φαινόμενο του πυρηνικού μαγνητικού συντονισμού. Στην κατηγορία της ποσοτικής ΑΜΣ (πΑΜΣ), όμως, μετράμε άμεσα τις ποσοτικές παραμέτρους από τις οποίες εξαρτώνται τα τελικά σήματα όπως χρόνους μαγνητικής αποκατάστασης, μοριακή διάχυση, pH, μικρο-ιξώδες κτλ. Η ρύθμιση και η βαθμονόμηση των παραμέτρων του τελικού μετρητικού συστήματος (σύστημα ΑΜΣ) παίζουν βασικό ρόλο στα τελικά αποτελέσματα των μετρήσεών μας. Για το λόγο αυτό είναι απαραίτητη η χρήση ειδικών ομοιωμάτων για τη βαθμονόμηση του μετρητικού συστήματος καθώς και για την αξιολόγηση και βελτιστοποίηση των μετρητικών μεθόδων. Τα ομοιώματα ελέγχου θα πρέπει να έχουν κάποια συγκεκριμένα βασικά χαρακτηριστικά, για να προσομοιάζουν όσο το δυνατόν καλύτερα τις μαγνητικά μετρούμενες παραμέτρους σε σχέση πάντα με εκείνες των ανθρωπίνων ιστών. Τέτοιες παράμετροι είναι κυρίως οι χρόνοι μαγνητικής αποκατάστασης (Τ1, Τ2, Τ2*) και η μοριακή διάχυση. Στα υλικά των ομοιωμάτων θα πρέπει να υπάρχει επιπλέον η δυνατότητα ανεξάρτητου ελέγχου των χρόνων μαγνητικής αποκατάστασης Τ1 και Τ2. Επίσης, θα πρέπει τα υλικά αυτά να έχουν φυσική και χημική σταθερότητα στο χρόνο και τέλος να παρασκευάζονται εύκολα και να είναι οικονομικά. Στην παρούσα εργασία παρασκευάστηκαν ειδικά ομοιώματα ενός πολυσακχαρίτη, της αγαρόζης, με πρόσμιξη μιας παραμαγνητικής ουσίας, του γαδολινίου (Gd-DTPA), σε 20 διαφορετικούς συνδυασμούς συγκεντρώσεων μεταξύ τους. Με βάση αυτά τα ομοιώματα μετρήσαμε τους χρόνους μαγνητικής αποκατάστασης Τ1, Τ2, Τ2* για οκτώ επαναλήψεις σε διάστημα τεσσάρων μηνών. Διαπιστώσαμε ότι η πιο αποτελεσματική ακολουθία για τη μέτρηση της Τ2 είναι σε μια ακολουθία πολλαπλών συμμετρικά επαναλαμβανόμενων Spin Echo (32 echo) με αρχική τιμή ΤΕ = 20ms. Με την χρήση της ακολουθίας αυτής καλύπτεται το μεγαλύτερο φάσμα μετρήσεων τιμών Τ2 για τους μαλακούς βιολογικούς ιστούς και επίσης τηρείται το 6 επιτρεπτό όριο του συντελεστή μεταβλητότητας για αυτόν τον τύπο των μετρήσεων (CV=±5%). Για τη μέτρηση της Τ1 εφαρμόσαμε δύο μεθόδους (Variable Flip Angle-VFA, Variable Time Inversion-VTI). Η πιο αποτελεσματική μέθοδος αποδείχθηκε η VTI. Η VFA υστερούσε στις μετρήσεις λόγω της αδυναμίας προσαρμογής των δεδομένων στην μαθηματική συνάρτηση περιγραφής των σημάτων λήψης Y(FA) = f (FA). Επιπλέον, διαπιστώσαμε ότι το παραμαγνητικό ιόν του γαδολινίου επηρεάζει την μέτρηση της Τ1 ανεξάρτητα από το μοριακό τύπο ή το είδος της χειλικής χημικής ένωσης στην οποία ανήκει. Τέλος, διαπιστώσαμε ότι σε όλες τις μετρήσεις η μεγαλύτερη ανομοιογένεια του τοπικού μαγνητικού πεδίου παρουσιάζεται στα πυκνά διαλύματα σε αγαρόζη και γαδολίνιο κυρίως λόγω της παραμαγνητικής ιδιότητας του γαδολινίου, η οποία επηρεάζει το τοπικό μαγνητικό πεδίο της μέτρησης. Μεγάλο συντελεστή μεταβλητότητας στις μετρήσεις της ανομοιογένειας του τοπικού μαγνητικού πεδίου παρουσιάζουν τα αραιά κολλοειδή διαλύματα και το νερό, διότι επηρεάζονται ευκολότερα από τις εξωτερικές επιδράσεις της μέτρησης (π.χ. θερμοκρασία) εξαιτίας της ασθενούς σύνδεσης μεταξύ των μορίων του υλικού τους. / The typical Magnetic Resonance Imaging (MRI) is based in the phenomenon of the nuclear magnetic resonance where each individual word, helps us understand its origin. Specifically, the measured signal is generated by the nucleus of the matter's atoms. The interaction of the latter is magnetic and the final signal is detected in the form of spectrum or images through the phenomenon of nuclear magnetic resonance. Nevertheless, in the field of quantitative MRI, we can measure quantitative parameters like magnetic relaxation time, molecular diffusion, micro-viscosity etc., on which the final signals depend. The adjustment and calibration of the parameters of the final metering systems (system MRI) are crucial for the final results. Therefore, it is essential to use special phantoms for the calibration of the metering system as well as for the valuation and optimization of the metering processes. The control phantoms need to have specific characteristics in order to simulate as much as possible the magnetically measured parameters with respect to the ones of the human tissues. Such parameters are mainly the magnetic relaxation times (T1, T2, T2*) and the molecular diffusion. The phantoms should also provide the option of individual testing of the magnetic relaxation times T1 and T2. Moreover, these materials should have the same physical and chemical stability in time and their production needs to be financially effective. In this paper, special agarose phantoms were produced, by mixing gadolinium, a paramagnetic substance, in 20 different concentrations. Based on these phantoms we measured 8 times the magnetic relaxation times Τ1, Τ2, Τ2* within a period of 4 months. We noted that the most effective sequence for measuring T2 is by symmetrically spin echo sequence with the initial time having the value of 20ms. Using this method, the widest range of T2 values is covered with regards to soft tissues. Additionally, the variation coefficient permissible figures for such measurements is respected (CV=±5%). In order to measure T1 we used two methods, Variable Flip Angle-VFA, Variable Time Inversion-VTI. The most effective one, was proven to be the VTI one. VFA method was presenting delays in the measurements due to the inability to adjust the data in the function of signal reception description Y(FA) = f (FA). Moreover, we discovered that the paramagnetic ion of gadolinium is affecting the measurement of T1 regardless the molecular type or the type of chemical ligand that this belongs to. Finally, we noted that throughout the experiments, the highest inhomogeneity of the local magnetic field is found in the dense solutions of agarose and gadolinium mainly due to the paramagnetic properties of gadolinium which affects the local magnetic field of the measurement. High variability factor of inhomogeneity of the local magnetic field demonstrated the dilute gels and water because of the poor connection between the molecules of their material.

[ES] La fabricación de nanopartículas con tamaños por debajo de los 100 nm ha permitido el desarrollo de innovadores nanodispositivos capaces de interactuar de forma directa con sistemas vivos a nivel celular y molecular, convirtiéndose en una parte fundamental dentro del campo de la nanomedicina. Uno de los principales retos a los que se enfrenta la ingeniería de nanopartículas es el desarrollo de nanodispositivos con propiedades físico-químicas bien definidas, ya que de ellas depende el comportamiento y biodistribución de dichos sistemas una vez introducidos en el organismo. No menos importante es el desarrollo de protocolos de síntesis reproducibles y optimizados, indispensables para la fabricación y escalado de nanodispositivos que puedan ser trasladados a futuras aplicaciones biomédicas. El principal objetivo de este proyecto de doctorado es el estudio y fabricación de nanopartículas magnéticas mesoporosas de sílice con estructura "core-shell" para su aplicación como agentes teranósticos en el campo de la nanomedicina. En este estudio se analiza en profundidad la síntesis y caracterización de dichos nanomateriales con el objetivo de producir nanopartículas con unas propiedades físico-químicas bien definidas de forma controlada y reproducible. La obtención de dichas nanopartículas supondría un gran avance de cara al desarrollo de nanodispositivos más complejos y sofisticados. El contenido de la tesis se ha estructurado en distintos capítulos que se detallan brevemente a continuación: ¿El capítulo 1 es una introducción a la nanomedicina, destacando el papel fundamental que tienen las nanopartículas en el desarrollo de nuevas aplicaciones biomédicas. A continuación se presentan las nanopartículas de sílice mesoporosa, mostrando la gran versatilidad de dichos nanomateriales para el desarrollo de dispositivos teranósticos así como sistemas para la liberación controlada de fármacos. Por último, se destaca la importancia de fabricar nanodispositivos con unas propiedades físico-químicas bien definidas como requisito indispensable para la traslación de los resultados experimentales hacia el campo clínico. ¿El capítulo 2 incluye los objetivos principales de la tesis. ¿El capítulo 3 se centra en la síntesis y caracterización de nanopartículas superparamagnéticas de óxido de hierro (USPIONs), siendo estas utilizadas en capítulos posteriores para la síntesis de las nanopartículas mesoporosas tipo "core-shell". Las USPIONs son preparadas a través de un método sencillo de coprecipitación en el que se emplean condiciones de reacción moderadas. Las nanopartículas obtenidas son caracterizadas en profundidad, analizando sus propiedades magnéticas para su aplicación en hipertermia magnética y como agentes de contraste dual en imagen por resonancia magnética (MRI). ¿El capítulo 4 está dedicado a la preparación de nanopartículas magnéticas mesoporosas de sílice con estructura "core-shell". Los conceptos fundamentales relacionados con los mecanismos de formación de este tipo de nanomateriales son ampliamente analizados, así como los parámetros de reacción involucrados en la síntesis. Como punto de partida, se propone un protocolo de síntesis general para la obtención de las nanopartículas tipo "core-shell". A continuación, se analiza en profundidad el efecto que los distintos parámetros de reacción tienen en las propiedades físico-químicas de dichas nanopartículas. Para la fase de optimización se utiliza un modelo semi-empírico como referencia, racionalizando los resultados experimentales observados en base a un posible mecanismo de formación. ¿El capítulo 5 se centra en el análisis y caracterización de la estructura mesoporosa de las nanopartículas tipo "core-shell". Además, se analiza el efecto que los distintos parámetros de reacción tienen sobre la estructura final de las nanopartículas, aportando información adicional sobre su posible mecanismo / [CAT] La fabricació de nanopartícules amb grandàries per davall dels 100 nm ha permés el desenvolupament d'innovadors nanodispositius capaços d'interactuar de forma directa amb sistemes vius a nivell cel¿lular i molecular, convertint-se en una part fonamental dins del camp de la nanomedicina. Un dels principals reptes als quals s'enfronta l'enginyeria de nanopartícules és el desenvolupament de nanodispositius amb propietats físic-químiques ben definides, ja que d'elles depén el comportament i biodistribució d'aquests sistemes una vegada introduïts en l'organisme. No menys important és el desenvolupament de protocols de síntesis reproduïbles i optimitzats, indispensables per a la fabricació a gran escala de nanodispositius que puguen ser utilitzats en futures aplicacions biomèdiques. El principal objectiu d'aquest projecte de doctorat és l'estudi i fabricació de nanopartícules magnètiques mesoporoses de sílice amb estructura "core-shell" per a la seua aplicació com a agents teranòstics en el camp de la nanomedicina. En aquest estudi s'analitza en profunditat la síntesi i caracterització d'aquests nanomaterials amb l'objectiu de produir nanopartícules amb unes propietats físic-químiques ben definides de forma controlada i reproduïble. L'obtenció d'aquestes nanopartícules suposaria un gran avanç de cara al desenvolupament de nanodispositius més complexos i sofisticats. El contingut de la tesi s'ha estructurat en diferents capítols que es detallen breument a continuació: ¿El capítol 1 és una introducció a la nanomedicina, destacant el paper fonamental que tenen les nanopartícules en el desenvolupament de noves aplicacions biomèdiques. A continuació es presenten les nanopartícules de sílice mesoporosa, mostrant la gran versatilitat d'aquests nanomaterials per al desenvolupament de dispositius teranòstics així com sistemes per a l'alliberament controlat de fàrmacs. Finalment, es destaca la importància de fabricar nanodispositius amb unes propietats físic-químiques ben definides com a requisit indispensable per a la translació dels resultats experimentals al camp clínic. ¿El capítol 2 inclou els objectius principals de la tesi així com els objectius específics proposats per a cada capítol de la tesi. ¿El capítol 3 està dedicat a la síntesi i caracterització de nanopartícules superparamagnétiques d'òxid de ferro (USPIONs), sent aquestes utilitzades en capítols posteriors per a la síntesi de les nanopartícules mesoporoses tipus "core-shell". Les USPIONs són preparades a través d'un mètode senzill de coprecipitació en el qual s'empren condicions de reacció moderades. Les nanopartícules obtingudes són caracteritzades en profunditat, analitzant les seues propietats magnètiques per a la seua aplicació en hipertèrmia magnètica i com a agents de contrast dual en imatge per ressonància magnètica (MRI). ¿El capítol 4 està dedicat a la preparació de nanopartícules magnètiques mesoporoses de sílice amb estructura "core-shell". Els conceptes fonamentals relacionats amb els mecanismes de formació d'aquest tipus de nanomaterials són àmpliament analitzats, així com els paràmetres de reacció involucrats en la síntesi. Com a punt de partida, es proposa un protocol de síntesi general per a l'obtenció de les nanopartícules tipus "core-shell". A continuació, s'analitza en profunditat l'efecte que els diferents paràmetres de reacció tenen en les propietats físic-químiques d'aquestes nanopartícules. Per a la fase d'optimització s'utilitza un model semi-empíric com a referència, racionalitzant els resultats experimentals observats sobre la base d'un possible mecanisme de formació. ¿El capítol 5 està dedicat a l'anàlisi i caracterització de l'estructura mesoporosa de les nanopartícules tipus "core-shell". A més, s'analitza l'efecte que els diferents paràmetres de reacció tenen sobre l'estructura final de les nanopartícules, aportant informació / [EN] The fabrication of nanoparticles with sizes below 100 nm has opened the door to the development of innovative nanodevices that directly interact with living systems at the cellular and molecular level, becoming an essential part of nanomedicine. One of the main challenges that nanoparticle engineering is currently facing is the design of nanodevices with well-defined physico-chemical properties, which ultimately determine the fate and function of these systems inside the organism. Similarly, the development of reproducible and versatile synthetic protocols is of great importance for manufacture purposes, a fundamental requirement for an efficient translation of this technology into the clinic. The main objective of this PhD thesis is the study and fabrication of core-shell-type magnetic mesoporous silica nanoparticles (M-MSNs) for their application as theranostic nanodevices in the field of nanomedicine. A comprehensive study about the synthesis and characterization of this type of nanomaterials is presented with the aim of obtaining core-shell M-MSNs with well-defined physico-chemical properties in a robust and reproducible way. The fabrication of such particles would provide a versatile and reliable platform for the development of more complex nanodevices with advanced functionalities. The thesis has been structured into several chapters that are briefly summarized as follows: ¿Chapter 1 is an introduction to the topic of nanomedicine, highlighting the importance of nanoparticles in the development of new biomedical applications. Mesoporous silica nanoparticles are then introduced, showing the great versatility that this nanomaterials offer for the development of theranostic nanodevices and smart drug delivery systems. Finally, the development of nanodevices with well-defined physico-chemical properties is identified as a crucial requirement for overcoming biological barriers and facilitate the translation of nanomedicines from the bench to bedside. ¿Chapter 2 presents the aims of this thesis and the specific objectives that are addressed in the following chapters. ¿Chapter 3 is devoted to the synthesis and characterization of ultrasmall superparamagnetic iron oxide nanoparticles (USPIONs), which are later used as magnetic seeds for the synthesis of core-shell M-MSNs. USPIONs are prepared through a simple coprecipitation method using mild reaction conditions. The obtained nanoparticles are fully characterized and their magnetic properties are analyzed focusing on magnetic hyperthermia and dual MR imaging applications. ¿Chapter 4 is a comprehensive study about the preparation of monodisperse core-shell M-MSNs. The main concepts related to the synthesis and formation mechanisms of this type of nanomaterials are revised, together with the reaction parameters that are expected to have a major contribution on the reaction. As a starting point, a general synthetic protocol for the synthesis of core-shell M-MSNs is presented. Then, specific reaction parameters are investigated in order to understand their effect on the physico-chemical properties of the obtained nanoparticles. The application of a semi-empirical model to the optimization stage is presented in an attempt to provide an adequate reference framework to understand the formation of this complex nanodevices. ¿Chapter 5 presents a detailed analysis about the characterization of mesoporous silica materials and, in particular, the assessment of the mesoporous structure of MSNs with a radial distribution of wormhole-like channels. The effects that specific reaction parameters have on the mesoporous silica structure of core-shell M-MSNs are also analysed, providing additional information about the formation of this type of nanoparticles. ¿Chapter 6 gathers the main conclusions of this thesis. / Sánchez Cabezas, S. (2019). Development of a reproducible and optimized synthetic protocol for the preparation of monodisperse core-shell-type magnetic mesoporous silica nanoparticles [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/129878 / TESIS

Understanding molecular and ion dynamics in soft materials used for fuel cell, battery, and drug delivery vehicle applications on multiple time and length scales provides critical information for the development of next generation materials. In this dissertation, new insights into transport and kinetic processes such as diffusion coefficients, translational activation energies (Ea), and rate constants for molecular exchange, as well as how these processes depend on material chemistry and morphology are shown. This dissertation also aims to serve as a guide for material scientists wanting to expand their research capabilities via nuclear magnetic resonance (NMR) techniques. By employing variable temperature pulsed-field-gradient (PFG) NMR diffusometry, which can probe molecular transport over nm – μm length scales, I first explore transport and morphology on a series of ion-conducting materials: an organic ionic plastic crystal, a proton-exchange membrane, and a polymer-gel electrolyte. These studies show the dependencies of small molecule and ion transport on modulations to material parameters, including thermal or magnetic treatment, water content, and/or crosslink density. I discuss the fundamental significance of the length scale over which translational Ea reports on these systems (~ 1 nm) and the resulting implications for using the Arrhenius equation parameters to understand and rationally design new ion-conductors. Next, I describe how NMR spectroscopy can be utilized to investigate the effect of loading a small molecule into the core of a spherical block copolymer micelle (to mimic, e.g., drug loading) on the hydrodynamic radius (rH) and polymer chain dynamics. In particular, I present spin-lattice relaxation (T1) results that directly measure single chain exchange rate kexch between micelles and diffusion results that inform on the unimer exchange mechanism. These convenient NMR methods thus offer an economical alternative (or complement) to time-resolved small angle neutron scattering (TR-SANS). / Ph. D.

Nuclear magnetic resonance (NMR) has become an effective borehole measurement option to assess petrophysical and fluid properties of porous and permeable rocks. In the case of fluid typing, two-dimensional (2D) NMR interpretation techniques have advantages over conventional one-dimensional (1D) interpretation as they provide additional discriminatory information about saturating fluids and their properties. However, often there is ambiguity as to whether fluids detected with NMR measurements are mobile or residual. In some instances, rapid vertical variations of rock properties (e.g. across thinly-bedded formations) can make it difficult to separate NMR fluid signatures from those due to pore-size distributions. There are also cases where conventional fluid identification methods based on resistivity and nuclear logs indicate dominant presence of water while NMR measurements indicate presence of water, hydrocarbon, and mud filtrate. In such cases, it is important to ascertain whether existing hydrocarbons are residual or mobile. The radial lengths of investigation of resistivity, nuclear, and NMR measurements are very different, with NMR measurements being the shallowest sensing. Even in the case of several radial zones of NMR response attributed to different acquisition frequencies and DC magnetic field gradients, the measured signal originates from a fairly shallow radial zone compared to that of nuclear and resistivity logs. Depending on drilling mud being used and the radial extent of mud-filtrate invasion, the NMR response of virgin reservoir fluids can be masked by mud filtrate because of fluid displacement and mixing. In order to separate those effects, it is important to reconcile NMR measurements with electrical and nuclear logs for improved assessment of porosity and mobile hydrocarbon saturation. Previously, Voss et al. (2009) and Gandhi et al. (2010) introduced the concept of Common Stratigraphic Framework (CSF) to construct and validate multi-layer static and dynamic petrophysical models based on the numerical simulation of well logs. In this thesis, the concept of CSF is implemented to reconcile 2D NMR interpretations with multi-layer static and dynamic petrophysical models. It is found that quantifying the exact radial zone of response and corresponding fluid saturations can only be accomplished with studies of mud-filtrate invasion that honor available resistivity and nuclear logs. This thesis indicates that the two interpretation methods complement each other and when applied in conjunction, improve and refine the overall petrophysical understanding of permeable rock formations. Examples of successful application include field data acquired in thinly-bedded gas formations invaded with water-base mud, where bed-boundary effects are significant and residual hydrocarbon saturation is relatively high. In such cases, numerical simulation of mud-filtrate invasion and well logs acquired after invasion enables reliable interpretations of petrophysical and fluid properties. The interpretation procedure introduced in this thesis also provides an explicit way to determine the uncertainty of petrophysical and fluid interpretations. / text

This dissertation deals with quantitative perfusion analysis of MRI contrast-enhanced image time sequences. It focuses on two so far separately used methods -- Dynamic contrast-enhanced MRI (DCE-MRI) and Dynamic susceptibility contrast MRI (DSC-MRI). The common problem of such perfusion analyses is the unreliability of perfusion parameters estimation. This penalizes usage of these unique techniques on a regular basis. The presented methods are intended to improve these drawbacks, especially the problems with quantification in DSC in case of contrast agent extravasation and instability of the deconvolution process in DCE using advanced pharmacokinetic models. There are a few approaches in literature combining DCE and DSC to estimate new parameters of the examined tissue, namely the relaxivity of the vascular and of the interstitial space. Originally, in this scheme, the 2CXM DCE model was used. Here various models for DCE analysis are tested keeping in mind the DCE-DSC combination. The ATH model was found to perform better in this setting compared to 2CXM. Finally, the ATH model was used in alternating DCE-DSC optimization algorithm and then in a truly fully simultaneous DCE-DSC. The processing was tested using simulated and in-vivo data. According to the results, the proposed simultaneous algorithm performs better in comparison with sequential DCE-DSC, unleashing full potential of perfusion analysis using MRI.