En oncologie ORL, l'imagerie multiparamétrique est utilisée par un nombre grandissant d'équipes. Parmi les bio-marqueurs, la captation normalisée du fluoro-désoxyglucose (SUV-FDG) en tomoscintigraphie par émission de positons (TEP) et la restriction de la diffusion en IRM (DWI-MRI) sont les plus utilisées.L'IRM couplée à la TEP (TEP/IRM) est une nouveauté qui permet une diminution très significative des doses d'irradiation délivrées par rapport à la TEP/TDM. Nous adressons notre première expérience concernant l'aspect en diffusion et en TEP/IRM dans la surveillance des patients après radio-chimiothérapie. A la question de l'interchangeabilité du FDG-PET et de la DWI-MRI, nous avons tenté d'identifier un lien en imagerie entre la cellularité tumorale et sa consommation glucidique. La cellularité tumorale est approchée en IRM par la mesure du coefficient apparent de diffusion (ADC) et son métabolisme glucidique est approché en TEP en utilisant le 18F-desoxyglucose (FDG) par la mesure de la valeur de fixation normalisée (SUV). Dans une série appariée de 33 patients, nous avons analysé la reproductibilité des mesures de l'ADC et de SUV. Puis nous avons évalué l'indépendance statistique de ces biomarqueurs. Nous avons ensuite voulu comparer les résultats de la TEP obtenus à partir de la TEP/TDM et de la TEP/IRM. Dans une série prospective appariée chez 32 patients explorés en FDG-TEP, nous avons évalué qualitativement les images obtenues par la fusion des images recalées en TEP/IRM et TEP/TDM. Nous avons ensuite comparé la pertinence clinique des deux techniques. Et enfin nous avons comparé les valeurs quantitatives de SUV obtenues du tissu sain et du tissu pathologique. / Multiparametric imaging interest and clinical use is rising for head and neck carcinoma (HNC). Among these modalities, FDG in PET and DWI-MRI are the most studied. PET/MRI is a new modality that allows in a single examination of combined various biologic biomarkers.After an optimization process of PET/MRI, we applied our first experience concerning the aspects of DWI-MRI and PET-MRI after radiation therapy. Thereafter we studied the correlation of SUV and ADC in HNC. In this study SUV and ADC values were independent parameters in HNSCC. Measurements of these two biomarkers were reproducible with almost perfect observer agreements for both methods. Neither SUV nor ADC values were able to predict the histologic grade, although a trend towards higher SUV and lower ADC values was observed in poorly differentiated tumours. Secondly, we we studied detection and quantification of focal uptake in head and neck tumours: 18F-FDG PET/MRI versus PET/CT in 32 consecutive HNSCC who underwent 18F-FDG PET/MRI and PET/CT. Attenuation correction sequence for PET/MRI and CT for PET/CT were used to caculate SUV. In results, PET/MRI coregistration and image fusion was feasible in all patients. There was no statistically significant difference between PET/MRI and PET/CT regarding rating scores for image quality, fusion quality, lesion conspicuity or anatomic location, number of detected lesions and number of patients with and without malignant lesions. A high correlation was observed for SUV measured on PET/MRI and PET/CT. SUV measured on PET/MRI were significantly lower than on PET/CT for malignant tumours, metastatic neck nodes, benign lesions, bone marrow, and liver (p <0.05).

L'objectif de cette thèse est de développer et d'évaluer des paramètres quantitatifs de l'IRM de la prostate en discriminant les cancers de score de Gleason (GS) ≥7. Nous supposons que les paramètres quantitatifs de l'IRM pourraient aider à standardiser le diagnostic, et à diminuer la variation inter-lecteur et/ou inter-institution du diagnostic du cancer de la prostate. Cette thèse est divisée en trois chapitres. Le premier chapitre, intitulé « IRM T2 quantitatif de la prostate », est une étude rétrospective sur une base de données des patients avant prostatectomie radicale. Le deuxième chapitre, intitulé « IRM multiparamétrique quantitative de la prostate », est aussi une étude rétrospective avant prostatectomie radicale. Le troisième chapitre, intitulé « Élastographie IRM de la prostate par voie trans-périnéale» est une étude expérimentale. Notre première étude montre que le T2 est robuste sur les machines de constructeurs différents. Le T2 est un prédicteur significatif, mais de faible performance, d'agressivité du cancer de la prostate à 3T. Notre deuxième étude montre que la combinaison du 10ème centile de l'ADC avec le Time-topeak (TTP) améliore la performance du diagnostic, et ce modèle est lui aussi robuste entre des machines de constructeurs différents. Notre troisième étude montre les résultats préliminaires sur l'élasticité de la prostate. Ces résultats montrent que l'élastographie IRM de la prostate en haute fréquence d'excitation (>100 Hz) par voie trans-périnéale est faisable. L'élastographie pourrait à l'avenir être intégrée à l'IRM multiparamétrique quantitative pour améliorer la performance de diagnostic / The purpose of this thesis is to develop and evaluate the quantitative methods of multiparametric MRI of prostate in discriminating Gleason score (GS) ≥7 cancers. We suppose that the quantitative parameter of MRI could help standardizer the diagnostic, reduce the inter-lecture and/ or inter-institution variation in diagnostic of prostate cancer. This thesis is divided into three chapters. The firs chapter, entilted « Quantitative T2 MRI of prostate » is a retrospective study on a database of prostate cancer patients before radical prostatectomy. The second chapter, entilted « Multi-parametric Quantitative MRI of prostate » is also a retrospective study before radical prostatectomy. The third chapter, entitled « MR elastography of prostate by transperineal approach », is an experimental study. Our first study shows that T2 value is robust between machines of different constructors. T2 value is significant predictor, but of weak performance, of aggressively cancer of prostate at 3T. Our second study shows that the combination of ADC_10th percentile with Time-to-peak (TTP) improved the diagnosis performance, and this model is also robust between two machines of different constructors. Our third study shows the initial results on elasticity of the prostate. These results show that MRI elastography of prostate at high excitation frequency (>100 Hz) by trans-perineale approach was feasible. The elastography may, in the future, be integrated in quantitative multi-parametric MRI to improve the diagnosis performance

Introduction: Targeted biopsy of tumour-suspicious lesions detected in multiparametric magnetic resonance imaging (mpMRI) plays an increasing role in the active surveillance (AS) of patients with low-risk prostate cancer (PCa). The aim of this study was to compare MRI/ultrasound-fusion biopsy (fusPbx) with systematic biopsy (sysPbx) in patients undergoing biopsy for AS. Methods: Patients undergoing mpMRI and transperineal fusPbx combined with transrectal sysPbx (comPbx) as surveillance biopsy were investigated. The detection of Gleason score upgrading and reclassification according to Prostate Cancer Research International Active Surveillance criteria were evaluated. Results: Eighty-three patients were enrolled. PCa upgrading was detected in 39% by fusPbx and in 37% by sysPbx (p = 1.0). The percentage of patients who were reclassified in fusPbx and sysPbx (p = 0.45) were 64 and 59% respectively. ComPbx detected more frequently tumour upgrading than fusPbx (71 vs. 64%, p = 0.016) and sysPbx (71 vs. 59%, p < 0.001) and more patients had to be reclassified after comPbx than after fusPbx or sysPbx alone. Conclusions: The combination of fusPbx and sysPbx outperforms both modalities alone with regard to the detection of upgrading and reclassification in patients under AS. Because a high missing rate of significant PCa still exists in both biopsy modalities, a combination of fusPbx and sysPbx should be recommended in these patients.

Objectives: We compared the transperineal MRI/ultrasoundfusion biopsy (fusPbx) to transrectal systematic biopsy (sys-Pbx) in patients with previously negative biopsy and investigated the prediction of tumour aggressiveness with regard to radical prostatectomy (RP) specimen. Material and Methods: A total of 710 patients underwent multiparametric magnetic resonance imaging (mpMRI), which was evaluated in accordance with Prostate Imaging Reporting and Data System (PI-RADS). The maximum PI-RADS (maxPI-RADS) was defined as the highest PI-RADS of all lesions detected in mpMRI. In case of proven prostate cancer (PCa) and performed RP, tumour grading of the biopsy specimen was compared to that of the RP. Significant PCa (csPCa) was defined according to Epstein criteria. Results: Overall, scPCa was detected in 40% of patients. The detection rate of scPCa was 33% for fusPbx and 25% for sysPbx alone (p < 0.005). Patients with a maxPI-RADS ≥3 and a prostate specific antigen (PSA)-density ≥0.2 ng/mL2 harboured more csPCa than those with a PSA-density < 0.2 ng/mL2 (41% [33/81] vs. 20% [48/248]; p < 0.001). Compared to the RP specimen (n = 140), the concordance of tumour grading was 48% (γ = 0.57), 36% (γ = 0.31) and 54% (γ = 0.6) in fusPbx, sysPbx and comPbx, respectively. Conclusions: The combination of fusPbx and sysPbx outperforms both biopsy modalities in patients with re-biopsy. Additionally, the PSA-density may represent a predictor for csPCa in patients with maxPI-RADS ≥3.

The goal of the thesis was applying multiparametric diagnostics to determine the state and wear of a high-speed milling machine. In the theoretical section, selected areas of multiparametric diagnostics have been described as well as a significant focus on vibrodiagnostics. The chosen methods for the practical section were incorporated into the group “metrological diagnostics”. Several different types of measurements have been performed on the designed test piece. The measurements were analyzed and lead to these specific results: a drawing of the test piece, a structured methodology for evaluating the test piece, recommendations for diagnostics of the specific machine, and proposals for the future development of the field of metrological diagnostics.

The thesis is focused on multiparametric diagnostic of generators at the Dukovany nuclear power plant. One generator was chosen for the thesis and it was examined especially from the practical point of view. The thesis describes current state of the issue with focus on noise diagnostics, vibrodiagnostics and electrodiagnostics. The emphasis is on the system approach of the solution. In the practical part an experiment is designed, described and evaluated. Attention is paid to the conclusions of the performed vibrodiagnostics and noise diagnostics. Data sets are evaluated separately and the relationship between the two diagnostic methods is analyzed. Furthermore, the data set from electrodiagnostics is evaluated and dependencies of electrical diagnostic quantities on other quantities are described. Trends in electrical diagnostic quantities are also monitored. Conclusions and recommendations are formulated at the end of the thesis. It is stated that using multiparametric diagnostics to assess the status of generators in power plants is still in its beginning and that the conclusions of the submitted thesis will contribute to the developmnet in this area.

Confronted with the global demographic changes and the increasing pressure on modern healthcare system, there has been a surge of developing new technology platforms in the past decades. Droplet microfluidics is a prominent example of such technology platforms, which offers an efficient format for massively parallelized screening of a large number of samples and holds great promise to boost the throughput and reduce the costs of modern biomedical activities. Despite recent achievements, the realization of a compact and generic screening system which is suited for resource-limited settings and point-of-care applications remains elusive. To address the above challenges, the dissertation focuses on the development of a compact multifunctional droplet micro-magnetofluidic system by exploring the advantages of magnetic in-flow detection principles. The methodologies behind a novel technique for biomedical applications, namely, magnetic in-flow cytometry have been put forth, which encompass magnetic indexing schemes, quantitative multiparametric analytics and magnetically-activated sorting. A magnetic indexing scheme is introduced and intrinsic to the magnetofluidic system. Two parameters characteristic of the magnetic signal when detecting magnetically functionalized objects, i.e. signal amplitude and peak width, providing information which is necessary to perform quantitative analysis in the spirit of optical cytometry has been proposed and realized. Magnetically-activated sorting is demonstrated to actively select individual droplets or to purify a population of droplets of interest. Together with the magnetic indexing scheme and multiparametric analytic technique, this functionality synergistically enables controlled synthesis, quality administration and screening of encoded magnetic microcarriers, which is crucial for the practical realization of magnetic suspension arrays technologies. Furthermore, to satisfy the needs of cost-efficient fabrication and high-volume delivery, an approach to fabricate magnetofluidic devices on flexible foils is demonstrated. The resultant device retains high performance of its rigid counterpart and exhibits excellent mechanical properties, which promises long-term stability in practical applications.

El análisis y el control de las vibraciones cobra especial importancia en muchas ramas de la ingeniería, en especial la ingeniería mecánica, civil, aeronáutica y automovilística. Tal es así que prácticamente se identi¿ca como un área independiente dentro del análisis dinámico de estructuras. Desde los comienzos de esta teoría, las fuerzas disipativas o de amortiguamiento han sido uno de los fenómenos más difíciles de modelizar. El modelo viscoso, por su sencillez y versatilidad ha sido y sigue siendo el gran paradigma de los modelos de amortiguamiento. Sin embargo, como consecuencia de la aparición de materiales con memoria se introdujo el fenómeno de la viscoelasticidad; Esta, si bien está también 'íntimamente ligada ' a la velocidad de la respuesta, necesito de la introducción de las denominadas funciones hereditarias, que permiten poner a las fuerzas disipativas como función no solo de la velocidad instantánea sino de la historia de velocidades desde el comienzo del movimiento, de ahí el termino memoria. De forma natural, el avance teórico introducido en el modelo supone también una complicación computacional, pues donde antes teníamos un sistema lineal de ecuaciones diferenciales ahora tenemos un sistema de ecuaciones integro-diferenciales. El análisis de las vibraciones libres de los sistemas con amortiguamiento viscoelástico conduce a un problema nolineal de autovalores donde la característica principal es una matriz de amortiguamiento que depende de la frecuencia de excitación. El estudio de la solución de autovalores y autovectores de este problema es importante si se desean conocer los modos de vibración de la estructura o si se pretende obtener la respuesta en el dominio de la frecuencia del sistema. El objetivo fundamental de esta Tesis Doctoral es doble: Por un lado, profundizar en el conocimiento del problema de autovalores de sistemas viscoelásticos proponiendo para ello nuevos métodos numéricos de resolución. Por otro, desarrollar un nuevo modelo viscoso que, bajo ciertas condiciones, reproduzca la respuesta del modelo viscoelástico con su¿ciente aproximación. La Tesis se divide en ocho capítulos, de ellos el cuerpo principal se encuentra en los seis centrales (Capítulos 2 a 7. Todos ellos son artículos de investigación que, o bien han sido publicados, o bien están en proceso de revisión en revistas contenidas en el Journal Citation Reports (JCR). Por esta razón, todos los capítulos conservan la estructura intrínseca de un artículo, incluidas una introducción y una bibliografía en cada uno. Los cuatro primeros capítulos (Capítulos 2 a 5) se centran en el estudio del problema no lineal de autovalores. Se proponen dos metodologías de resolución: la primera es un procedimiento iterativo basado en el esquema del punto-¿jo y desarrollado para sistemas proporcionales o ligeramente no-proporcionales (aquellos en los que los modos se presentan desacoplados o casi desacoplados). La segunda metodología (presentada en dos capítulos diferentes), denominada paramétrica, permite obtener soluciones casi-analíticas de los autovalores, tanto para sistemas de un grado de libertad como para sistemas de múltiples grados de libertad y dentro de 'estos, para sistemas proporcionales y no proporcionales. El estudio del problema de autovalores se completa con un capítulo dedicado a los autovalores reales, también denominados autovalores no viscosos. En 'él se demuestra una nueva caracterización maten ática que deben cumplir dichos autovalores y que permite proponer un nuevo concepto: el conjunto no-viscoso. Los dos 'últimos capítulos (Capítulos 6 y 7) analizan el Modelo Viscoso Equivalente como propuesta para la modelización de la respuesta de sistemas viscoelásticos. El análisis se realiza desde el dominio de la frecuencia estudiando la función de transferencia. En una primera etapa (pen último capítulo), de naturaleza más maten ática, se demuestra que la función de transferencia exacta de un modelo viscoelástico se puede expresar como suma de una función de transferencia propia de un modelo viscoso más un término denominado residual, directamente dependiente del nivel de amortiguamiento inducido y del acoplamiento modal (noproporcionalidad de la matriz de amortiguamiento). En una segunda etapa ('ultimo capítulo), se desarrolla una aplicación para estructuras reales formadas por entramados planos de elementos 1D amortiguados con capas de material visco elástico. Este tipo de estructuras ha permitido usar una variante mejorada del método paramétrico para la obtención de los autovalores, de forma que en este 'ultimo capítulo ha servido como nexo de unión de las metodologías más importantes desarrolladas en la Tesis. / Lázaro Navarro, M. (2013). The Eigenvalue Problem in Linear Viscoelastic Structures: New Numerical Approaches and the Equivalent Viscous Model [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/30062 / TESIS

Objectives: The study aimed to evaluate the prediction of Prostate Imaging Reporting and Data System (PI-RADS) with respect to the prostate cancer (PCa) detection rate and tumor aggressiveness in magnetic resonance imaging (MRI)/ultrasound-fusion-biopsy (fusPbx) and in systematic biopsy (sysPbx). Materials and Methods: Six hundred and twenty five patients undergoing multiparametric MRI were investigated. MRI findings were classified using PI-RADS v1 or v2. All patients underwent fusPbx combined with sysPbx (comPbx). The lesion with the highest PI-RADS was defined as maximum PI-RADS (maxPI-RADS). Gleason Score ≥ 7 (3 + 4) was defined as significant PCa. Results: The overall PCa detection rate was 51% ( n = 321; 39% significant PCa). The detection rate was 43% in fusPbx ( n = 267; 34% significant PCa) and 36% in sysPbx ( n = 223; 27% significant PCa). Nine percentage of significant PCa were detected by sysPbx alone. A total of 1,162 lesions were investigated. The detection rate of significant PCa in lesions with PI-RADS 2, 3, 4, and 5 were 9% (18/206), 12% (56/450), 27% (98/358), and 61% (90/148) respectively. maxPI-RADS ≥ 4 was the strongest predictor for the detection of significant PCa in comPbx (OR 2.77; 95% CI 1.81–4.24; p < 0.005). Conclusions: maxPI-RADS is the strongest predictor for the detection of significant PCa in comPbx. Due to a high detection rate of additional significant PCa in sysPbx, fusPbx should still be combined with sysPbx.

La fibrillation auriculaire (FA) est le type d’arythmie cardiaque le plus fréquent. Cependant, ses mécanismes sont encore mal compris et le développement de stratégies thérapeutiques efficaces reste un défi. Des recherches ont montré que les mécanismes de remodelage structurel, notamment la dissociation électrique endocardique-épicardique, jouent un rôle potentiellement important dans l'initiation, la complexité et le maintien de la FA. En ce sens, les potentiels extracellulaires sont des outils non invasifs largement utilisés dans le diagnostic et la compréhension de cette arythmie ainsi que dans le guidage des interventions par cathéter. L'objectif principal de cette thèse était de développer des modèles informatiques des oreillettes et d’étudier dans ces modèles comment les potentiels extracellulaires et les cartes d'activation à haute résolution peuvent être exploités pour caractériser les mécanismes de dissociation endocardique-épicardique en tant que substrat de la FA. Dans un premier temps, en utilisant un modèle de tissu auriculaire, nous avons montré que la dissociation endo-épicardique (délai endo-épicardique et couplage transmural) affecte l'asymétrie des électrogrammes unipolaires à travers l'orientation des sources de courant dipolaire dans le tissu auriculaire. Ce résultat a été par la suite confirmé par l’analyse morphologique des composantes de l’onde P dans un modèle anatomique des oreillettes. Nous avons en outre montré que l’épaisseur de la paroi auriculaire ainsi que le couplage transmural étaient des déterminants importants de ce délai, et que ce dernier peut induire des altérations significatives de la morphologie l’onde P même lorsque les cartes d’activation sont similaires et que les ondes P ont la même durée. Dans un second temps, nous avons exploré les effets tridimensionnels de la dissociation endo-épicardique et validé une technique de détection de percée d’ondes (breakthroughs) basée sur l’analyse des cartes d'activation à haute résolution et le suivi des ondes, en utilisant un modèle électro-anatomique de découplage endo-épicardique local. Nous avons utilisé cet outil pour la caractérisation de la dissociation endo-épicardique. Un critère de validité en a été dérivé, ce qui faciliterait la comparaison des taux de percée avec les données cliniques et la validation des outils d'analyse des signaux cartographiques lors de la caractérisation de la dissociation endo-épicardique. Enfin, nous avons développé un outil d'optimisation multi-paramètre qui rend possible l’étude des limites des modèles continus homogénéisés dans l'étude des mécanismes de dissociation endo-épicardique et aide dans le choix des modèles (continu homogénéisé ou discret détaillé). L’outil permet d’estimer le profil régulier de conductivité qui reproduit le mieux les propriétés de conduction cardiaque d'un modèle discret donné. Les résultats ont montré l'efficacité de cet outil pour reproduire des cartes d'activation dans le modèle homogénéisé même en présence de fibrose sévère. Ultimement, ce travail pose les bases du développement de nouveaux modèles informatiques pouvant aider à l’interprétation des signaux électriques dans des tissus cardiaques remodelés où la présence de micro-hétérogénéités exhibe les limites des modèles homogénéisés. / Atrial fibrillation (AF) is the most common type of cardiac arrhythmia. However, its mechanisms are still poorly understood and the development of effective therapeutic strategies remains a challenge. Research studies have shown that the mechanisms of structural remodeling, including endocardial-epicardial electrical dissociation, play a potentially important role in the initiation, complexity, and maintenance of AF. In this sense, extracellular potentials are non-invasive tools widely used in the diagnosis and understanding of this arrhythmia as well as in the guidance of catheter interventions. The main objective of this thesis was to develop computer models of the atria and to study in these models how extracellular potentials and high resolution activation maps can be exploited to characterize the mechanisms of endocardial-epicardial dissociation as substrate of AF. First, using an atrial tissue model, we showed that endo-epicardial dissociation (endo-epicardial delay and transmural coupling) alters the asymmetry of unipolar electrograms through the orientation of dipolar current sources in the atrial tissue. This result was later confirmed by morphological analysis of the P-wave components in an anatomical model of the atria. We further showed that atrial wall thickness as well as transmural coupling were important determinants of this delay, and that the latter can induce significant alterations in P-wave morphology even when activation maps are similar and P-waves have the same duration. Secondly, we explored the three-dimensional effects of endo-epicardial dissociation and validated a breakthrough wave detection technique based on the analysis of high-resolution activation maps and wave tracking, using an electro-anatomical model of local endo-epicardial decoupling. We used this tool for the characterization of endo-epicardial dissociation. A validity criterion was derived, which would facilitate the comparison of breakthrough rates with clinical data and the validation of mapping signals analysis tools for characterizing endo-epicardial dissociation. Finally, we developed a multi-parameter optimization tool that makes it possible to study the limits of homogenized continuous models in the study of endo-epicardial dissociation mechanisms and to help in the choice of models (homogenized continuous or detailed discrete). The tool enabled the estimation of the regular conductivity profile that best reproduces the cardiac conduction properties of a given discrete model. The results showed the effectiveness of this tool in reproducing activation maps in the homogenized model even in the presence of severe fibrosis. Ultimately, this work lays the foundations for the development of new computer models that can help in the interpretation of electrical signals in remodeled heart tissues where the presence of micro-heterogeneities exhibits the limits of homogenized models.