Contributions to the quantitative analysis of dynamic PET studies using clustering approaches

Mención Internacional en el título de doctorDynamic positron emission tomography (PET) is a widespread medical imaging technique that allows the quantification of different physiological parameters within the body and yields more information that the one provided by a single, static image. Quantification of these studies involves obtaining the input function, that is, the amount of tracer present in arterial blood at any given point in time, and the tissue time-activity curve (TAC) for the tissue or organ under study. The subjacent biological processes are modelled as the tracer exchange rates between the arterial activity source and a compartmental model; this mathematical approach allows to quantify different biological aspects (metabolic rates, blood flow, specific receptor binding) in a non-invasive way. Typically, arterial and tissue TACs are extracted from the image data by drawing a ROI over the areas of interest, either over the PET image or over some anatomical imaging modality, such as CT, and in some cases acquire some blood samples to correct the input function for metabolites, partial volume effects or other different sources of distortion that may bias the final result. While this ROI delineation is done normally by an experienced operator, this process is very slow and, more importantly, subjective and non-replicable. Furthermore, ROI delineation over registered anatomical images may group together regions that look identical in the CT image but have different underlying kinetics. These reasons have motivated the development of automatic segmentation or TAC extraction algorithms, of which there are several examples in the medical imaging literature. Most of the proposed methods involve the use of unsupervised machine learning algorithms or the direct application of dimensionality reduction techniques, such as PCA or SVD. This thesis studies the feasibility of supervised algorithms to extract the activity curves of dynamic studies based solely on the knowledge acquired about the kinetics of similar ones. Our experiments on three swine studies showed that the segmentation was successful and the obtained TACs allowed the computation of the kinetic analysis and obtained smaller errors in the kinetic parameters obtained from the mathematical model than the manual segmentations. Said supervised algorithms are not common in the literature but we have shown that they can be a viable option for very specific subset of cases. One of the problems of the published automatic segmentation algorithms is the general lack of published source codes or even binary distributions. As has been studied in the literature, this presents a problem by itself, as it forces other researchers to re-implement said algorithms. This work presents the development of an open framework for dynamic imaging clustering that includes the most commonly used algorithms and that can be easily extended by third parties through the use of its public API. The code for said framework has been published with a free software license to allow it to be modified by external researchers and adapt it to their needs. It has been developed as an ImageJ plugin to take advantage to all the imaging analysis functionalities already presented in said platform. Using this framework, we also present an improvement of the classical leader-follower algorithm. This unsupervised algorithm groups image voxels with similar TACs according to a threshold set by the user and creates as many clusters as necessary to form homogeneous regions. Due to the nature of the partial volume distortions that need to be removed from the final TACs as much as possible, the proposed method implements a two-step leader-follower modification. In this case, the image voxels are clustered according to both a similarity metric and a distance metric; particularly, the cosine similarity and the Euclidean distance were chosen for our tests. This algorithm successfully segmented all of the evaluated 24 mice imaging studies, yielding quantitative parameters after the kinetic modelling that were not significantly different from those obtained via manual delineation and maintained the differences between the three tracers used in this experiment. --------------------------------------------------------La tomografía por emisión de positrones (PET) es una técnica de imagen médica ampliamente utilizada que permite la cuantificación de diferentes parámetros fisiológicos dentro del cuerpo y arroja más información que la que puede obtenerse mediante una única imagen estática. La cuantificación de estos estudios necesita la obtención de la función de entrada, esto es, la cantidad de trazador presente en sangre arterial a lo largo del tiempo, y la curva de actividad (TAC) del tejido u órgano bajo estudio. Los procesos biológicos subyacentes se modelan como las velocidades de intercambio de trazador entre la fuente de actividad arterial y un modelo compartimental; esta aproximación matemática permite cuantificar diferentes aspectos biológicos (metabolismo, flujo sanguíneo, fijación a receptores específicos) de una forma no invasiva. Típicamente, la función de entrada y la TAC de los tejidos se extraen directamente de la imagen mediante el trazado de una región de interés (ROI), bien sobre la imagen PET directamente o sobre alguna modalidad de imagen que presente información anatómica, como el CT, y en algunos casos requiere la obtención de muestras de sangre para corregir en la función de entrada el efecto de metabolitos, efectos de volumen parcial u otras fuentes de distorsión que pueden sesgar el resultado final. Aunque este proceso de delineación lo realiza habitualmente un operador experimentado, este proceso es lento, subjetivo y no replicable. Además, la delineación de ROIs sobre imágenes anatómicas registradas puede agrupar regiones que aparecen idénticas en la imagen de CT pero tienen diferentes comportamientos cinéticos. Estas razones han motivado el desarrollo de algoritmos de segmentación automática o extracción de TAC, de los cuales hay múltiples ejemplos en la literatura de imagen médica. La mayoría de los métodos propuestos son implementaciones de algoritmos de unsupervised machine learning, o aprendizaje máquina no supervisado, o la aplicación directa de técnicas de reducción de dimensionalidad, como análisis de componentes principales (PCA) o descomposición en valores singulares (SVD). Esta tesis doctoral estudia la posibilidad de emplear algoritmos supervisados para extraer las curvas de actividad de estudios dinámicos basándose únicamente en el conocimiento adquirido en la cinética de estudios similares. La experimentación con tres estudios porcinos mostró que la obtención de las TACs fue exitosa, y estos datos permitieron el cálculo de los parámetros cinéticos, obteniendo errores en el ajuste matemático menores que los obtenidos mediante una segmentación manual. Este tipo de algoritmos supervisados no son comunes en la literature pero hemos demostrado que pueden ser una opción viable para un subconjunto de casos específico. Uno de los problemas de los algoritmos de segmentación automática publicados en la literatura es la carencia general de código fuente o incluso distribuciones binarias. Como ya se ha estudiado en la literature, esto presenta un problema, al forzar a investigadores de otras instituciones a reimplementar dichos algoritmos. Este trabajo presenta un marco de desarrollo para algoritmos de clustering aplicados a imagen médica dinámica que incluye los algoritmos más comúnmente utilizados y que puede ser extendido fácilmente mediante terceros a través del uso de su interfaz de programación (API) pública. El código para dicho marco de desarrollo ha sido publicado con una licencia libre para permitir su modificación por investigadores externos y su adaptación a sus necesidades. Se ha programado como un plugin de la plataforma de análisis de imagen ImageJ para aprovechar todas las ventajas y funcionalidades de análisis ya presentes en dicha plataforma. Empleando este marco de desarrollo, finalmente presentamos una mejora sobre un algoritmo clásico leader-follower. Este algoritmo no supervisado agrupa vóxeles de la imagen con TACs similares de acuerdo a un umbral establecido por el usuario, y crea tantos clusters, o grupos, necesaarios para formar regiones homogéneas. Debido a los efectos de volumen parcial, que deben ser eliminados de las TACs finales lo máximo posible, el método propuesto implementa una modificación del leader-follower en dos pasos. En este caso, los vóxeles de la imagen se agrupan de acuerdo a una métrica de similitud (coseno) y una métrica de distancia (Euclídea). El algoritmo segmentó con éxito 24 imágenes dinámicas de ratón, ofreciendo parámetros cuantitativos tras el modelado cinético que no fueron diferentes de forma significativa de los obtenidos a través de la delineación manual y manteniendo las diferencias observadas entre los tres trazadores empleados en este experimento.Programa Oficial de Doctorado en Multimedia y ComunicacionesPresidente: María Jesús Ledesma Carbayo; Secretario: Jorge Ripoll Lorenzo; Vocal: Stephen L. Bacharac

Metropolitan Mobility In Spain Are We Tending Towards Sustainability?

There is a growing concern in the urban transport field about the development of a data set of indicators that would allow to undertake ongoing monitoring and evaluation of current transportation policies, compare data from territories facing the same kind of challenges, identify good practices and strategies to be followed, and strengthen the information, participation and decision-making process. These data set of indicators, known as observatories, are aimed to fulfil stakeholders needs, so that they achieve the precise knowledge to adopt pertinent policies. The Spanish Metropolitan Mobility Observatory, sponsored by the Spanish Ministry of Environment, was launched in 2003 by the Metropolitan Transport Authorities of the major metropolitan areas in Spain, and TRANSyT. Its scope is to identify those elements within urban transport policy packages which have had a more significant impact on mobility (i.e. global transport demand, travel time, modal split,…), and on land use patterns. And its main goal is to serve as basis for Metropolitan Transport Authorities to improve operation of their public transport system, and thus increasing their contribution to sustainable mobility. For itsFor its second edition, based on the year 2003, a set of data from the different Metropolitan Transport Authorities has been collected, in order to: Highlight public transport contribution to improve urban areas and sustainable development - Describe the role of Metropolitan Transport Authorities in achieving an attractive and quality public transport - Monitoring transport supply and demand characteristics, focusing on public transport - Analyse resources dedicated to the public transport system - Describe the financial models used for the public transport system - Highlight the main initiatives and innovations developed by Metropolitan areas This information will be compared to that one from the previous edition, and a statistical analysis will be conducted in order to identify those variables, which are likely to explainresults in most cities.Institute of Transport and Logistics Studies. Faculty of Economics and Business. The University of Sydne

Metropolitan Mobility In Spain Are We Tending Towards Sustainability?

Workshop FThere is a growing concern in the urban transport field about the development of a data set of indicators that would allow to undertake ongoing monitoring and evaluation of current transportation policies, compare data from territories facing the same kind of challenges, identify good practices and strategies to be followed, and strengthen the information, participation and decision-making process. These data set of indicators, known as observatories, are aimed to fulfil stakeholders needs, so that they achieve the precise knowledge to adopt pertinent policies. The Spanish Metropolitan Mobility Observatory, sponsored by the Spanish Ministry of Environment, was launched in 2003 by the Metropolitan Transport Authorities of the major metropolitan areas in Spain, and TRANSyT. Its scope is to identify those elements within urban transport policy packages which have had a more significant impact on mobility (i.e. global transport demand, travel time, modal split,…), and on land use patterns. And its main goal is to serve as basis for Metropolitan Transport Authorities to improve operation of their public transport system, and thus increasing their contribution to sustainable mobility. For itsFor its second edition, based on the year 2003, a set of data from the different Metropolitan Transport Authorities has been collected, in order to: Highlight public transport contribution to improve urban areas and sustainable development - Describe the role of Metropolitan Transport Authorities in achieving an attractive and quality public transport - Monitoring transport supply and demand characteristics, focusing on public transport - Analyse resources dedicated to the public transport system - Describe the financial models used for the public transport system - Highlight the main initiatives and innovations developed by Metropolitan areas This information will be compared to that one from the previous edition, and a statistical analysis will be conducted in order to identify those variables, which are likely to explainresults in most cities.Institute of Transport and Logistics Studies. Faculty of Economics and Business. The University of Sydne

Type of grinding of the main cereal of the diet affects production of brown egg-laying hens

The influence of method of grinding of the cereal of the diet on production and egg quality was studied in 420 Hy-line brown egg-laying hens. The design was completely randomized with six treatments arranged as a 3 × 2 factorial with three cereals (barley, dented maize and soft wheat) and two grinding procedures (hammer mill vs. roller mill). Each treatment was replicated seven times and the experimental unit was an enriched cage with ten hens. Production was recorded every four weeks from 24 to 59 weeks of age and egg quality was measured at 40 and 56 weeks of age. For the entire experiment, feed intake was higher in hens fed wheat or maize than in hens fed barley (110.8 and 110.7 vs. 109.7 g/d; P = 0.014) but most of the differences were observed when the cereal was roller milled (P = 0.009 for the interaction). Also, egg production was similar for the three diets when the cereal was hammer milled but tended to be lower for the barley than for the wheat or maize diets when the cereal was roller milled (P = 0.09 for the interaction). None of the other productive or egg quality traits was affected by dietary treatment. We conclude that roller mills are useful to grind low fiber cereals, such as maize or wheat. However, the use of the roller mill might not be adequate when barley is the main cereal in diets for egg-laying hens

Fracturas estallido de columna toracolumbar: Evaluación clinicoradiológica y terapéutica de 90 casos

Presentamos un estudio retrospectivo de 90 fracturas toracolumbares tipo estallido con un seguimiento mínimo de 12 meses. Se realizó tratamiento ortopédico en 43 casos y en 47 se indicó una artrodesis instrumentada. Realizamos una evaluación clínico-radiológica en base al dolor residual y evolución del ángulo de cifosis con el objetivo de valorar el tratamiento ortopédico como opción terapéutica y la necesidad de distinguir fracturas estallido con afectación de 2 ó 3 columnas. No apreciamos diferencias estables significativas en el dolor y la lesión de las tres columnas. El aumento de cifosis angular media en las fracturas estallido estable no operadas es de 4.7º y de 5.2º en las fracturas estallido inestables tratadas ortopédicamente. Observamos una alta incidencia de complicaciones relacionadas con la fijación (21%) cuando la fractura asentaba en la charnela y se instrumentaba a un solo nivel. El tratamiento ortopédico es una opción aceptable en las fracturas estallido en pacientes neurológicamente indemnes.Ninety burst fractures of the thoracolumbar spine were retrospectively assessed with a minum follow-up of 12 months. Conservative treatment was indicated in 43 cases, and reduction and surgical stabilization in 47. The aim was to compare the two treatment modalities according to fracture stability. Clinical and radiological evaluation included chronic pain and kyphotic angle progression. No statistical differences were found between stable and unstable fractures as to chronic pain. The kyphotic angle average progression for stable burst fractures was 4.7º and 5.2º for unstable fractures conservatively treated. There was a high rate of complications related to instrumentation (21%) particularly when the fracture was at the thoracolumbar junction and a single level was fixed. The orthopaedic treatment is an acceptable alternative treatment for stable burst fractures without neurological injury

Identification of Key Molecules Involved in the Protection of Vultures Against Pathogens and Toxins

This is an open access article distributed under the terms of the Creative Commons Attribution License.This work was supported by the Junta de Comunidades de Castilla-La Mancha (JCCM), project PII1I09-0243-4350.Peer Reviewe

A Maut aprroach for reusing domain ontologies on the basis of the NeOn Methodlogy

Knowledge resource reuse has become a popular approach within the ontology engineering field, mainly because it can speed up the ontology development process, saving time and money and promoting the application of good practices. The NeOn Methodology provides guidelines for reuse. These guidelines include the selection of the most appropriate knowledge resources for reuse in ontology development. This is a complex decision-making problem where different conflicting objectives, like the reuse cost, understandability, integration workload and reliability, have to be taken into account simultaneously. GMAA is a PC-based decision support system based on an additive multi-attribute utility model that is intended to allay the operational difficulties involved in the Decision Analysis methodology. The paper illustrates how it can be applied to select multimedia ontologies for reuse to develop a new ontology in the multimedia domain. It also demonstrates that the sensitivity analyses provided by GMAA are useful tools for making a final recommendation

A MAUT approach for reusing ontologies

Knowledge resource reuse has become a popular approach within the ontology engineering field, mainly because it can speed up the ontology development process, saving time and money and promoting the application of good practices. The NeOn Methodology provides guidelines for reuse. These guidelines include the selection of the most appropriate knowledge resources for reuse in ontology development. This is a complex decision-making problem where different conflicting objectives, like the reuse cost, understandability, integration workload and reliability, have to be taken into account simultaneously. GMAA is a PC-based decision support system based on an additive multi-attribute utility model that is intended to allay the operational difficulties involved in the Decision Analysis methodology. The paper illustrates how it can be applied to select multimedia ontologies for reuse to develop a new ontology in the multimedia domain. It also demonstrates that the sensitivity analyses provided by GMAA are useful tools for making a final recommendation

Síndrome del túnel radial: Epicondilitis resistente

Desde 1996 al 2003, fueron intervenidos 25 pacientes (26 extremidades) de síndrome del túnel radial. Todos los procedimientos fueron realizados por el mismo cirujano y en el mismo hospital con un abordaje postero-externo del túnel radial. Se realizó un seguimiento de todos los pacientes en el tiempo después de la cirugía de 4 meses a 6 años y 4 meses (tiempo medio de 22 meses). Los resultados fueron evaluados según los criterios de Roles y Mausdley; 12 pacientes tuvieron resultados excelentes (46.15%), 9 pacientes buenos (34.61%) y 5 pacientes regulares (19.23%). Once pacientes fueron tratados previamente de epicondilitis lateral (entesitis). La mayoría de los pacientes están satisfechos con la cirugía refiriendo un alivio de la sintomatología y una mejora de la funcionalidad tras la cirugía.Between 1996 and 2003, 25 patients (26 extremities) underwent decompression of the radial tunnel. All procedures were performed at the same surgeon and the same institution using posterior approach. The total 25 patients were available for follow-up evaluation alter surgery (range 4 months - 6 years and 4 months) with average of 22 months. The outcomes was determined using the original criteria of Roles and Mausdley, 12 patients were rated as excellent (46.15%), 9 patients has good results (34.61%) and 5 patients had fair results. Eleven patients were treated previously of tennis elbow. Most of the patients were satisfied and felt subjectively improved by the surgery. They obtained pain relief and better functional status after surgery

Segmentación automática de estudios PET cardíacos con ¹³NH_3 basada en correlación iterativa

Actas de: XXVIII Congreso Anual de la Sociedad Española de Ingeniería Biomédica (CASEIB 2010). Madrid, 24-26 de noviembre de 2010.La obtención de la función de entrada en estudios dinámicos de corazón a partir de la imagen PET se realiza habitualmente mediante la selección previa de una región de interés (ROI) o utilizando procedimientos de análisis factorial para encontrar aquellas curvas actividad/tiempo que mejor se adaptan a la función de entrada. En este trabajo se presenta un método novedoso de segmentación automática y obtención de la función de entrada que utiliza mapas de correlación calculados sobre estudios dinámicos que emplean ¹³NH_3 como trazador. Partiendo de un modelo analítico inicial, se buscan las curvas temporales más parecidas en el estudio real empleando la correlación. Tomando como datos estas curvas se calculan nuevos modelos con los que realizar sucesivas iteraciones. El resultado final es tanto una segmentación automática como la curva de actividad/tiempo de cada región segmentada.Ministerio de Ciencia e Innovación, TEC2007-64731, TEC 2008-06715-C02-1, la RETIC-RECAVA del Ministerio de Sanidad y Consumo, y el programa ARTEMIS S2009/DPI-1802 de la Comunidad de Madrid.Publicad