883 resultados para asymptotic local power
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Este artículo se propone analizar la forma en que se implantó la Justicia de Paz en el interior de la provincia de Buenos Aires entre 1865 y 1910, a través del estudio de los sujetos que desempeñaron esa función y los entramados políticos en los que participaron. El mismo se ha realizado a partir del estudio de un Juzgado en particular, como fue el del partido de Tres Arroyos. Por un lado, se reconstruye el perfil de los sujetos que ejercieron el cargo de Jueces de Paz, con la intención de entender las lógicas que guiaron su designación. Para ello, se indaga en la reconstrucción de sus biografías asociadas a los diversos momentos de ocupación e institucionalización local. Posteriormente se identifican dos modos de nucleamiento que sirvieron de base relacional a los individuos del lugar y que permiten completar la explicación generada desde las biografías individuales: una red de tipo iniciática, como fue la masonería; y una red del conservadurismo local, dirigida por poderosos estancieros del lugar. Por último, se observa si esas redes influyeron en la administración de justicia local. Las fuentes utilizadas son diversos álbumes conmemorativos locales, datos censales, periódicos locales, expedientes correccionales tramitados en la Justicia de Paz de Tres Arroyos, el Libro Copiador de Notas del Juzgado y el Libro de Actas de la Logia Hiram de Tres Arroyos.
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En la presente ponencia nos proponemos analizar la situación jurídica y política de algunos extranjeros que ocupaban cargos públicos o realizaban oficios civiles en el Rio de la Plata. En este contexto, los criterios para definir quién era un vecino-ciudadano dependían de la posibilidad de mantener o perder cargos públicos, o de ejercer ciertos oficios en los pueblos de la campaña. Se estudiarán dos casos en los cuales se presentaron situaciones análogas para los que no eran reconocidos pertenecientes a la comunidad política, es decir para los extranjeros. Aquellos que no lograban la obtención de una carta de ciudadanía se veían obligados a dejar sus cargos u oficios. Sin embargo, los reglamentos y las decisiones del gobierno en estos casos se vieron superados por las prácticas y situaciones concretas. Otro de los casos estudiados en esta ponencia se corresponde con un litigio en Chascomús un fuerte y pueblo de la campaña de Buenos Aires, en la frontera con el mundo indígena. Allí, un hombre de origen catalán le es impedido ejercer su oficio de panadero, limitándolo a la producción de pastelería fina. La decisión fue tomada por el comandante del fuerte ante un pedido de un grupo de panaderas que se consideraban 'patricias', señalando el origen español de dicho panadero para limitarlo en el ejercicio del oficio. El conflicto nos ofrece varias aristas interesantes sobre los mecanismos del ejercicio del poder que estamos viendo en otros trabajos, pero aquí nos detendremos en la definición del grupo de pertenencia y en la utilización de los conceptos de patria y patriotas
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En la presente ponencia nos proponemos analizar la situación jurídica y política de algunos extranjeros que ocupaban cargos públicos o realizaban oficios civiles en el Rio de la Plata. En este contexto, los criterios para definir quién era un vecino-ciudadano dependían de la posibilidad de mantener o perder cargos públicos, o de ejercer ciertos oficios en los pueblos de la campaña. Se estudiarán dos casos en los cuales se presentaron situaciones análogas para los que no eran reconocidos pertenecientes a la comunidad política, es decir para los extranjeros. Aquellos que no lograban la obtención de una carta de ciudadanía se veían obligados a dejar sus cargos u oficios. Sin embargo, los reglamentos y las decisiones del gobierno en estos casos se vieron superados por las prácticas y situaciones concretas. Otro de los casos estudiados en esta ponencia se corresponde con un litigio en Chascomús un fuerte y pueblo de la campaña de Buenos Aires, en la frontera con el mundo indígena. Allí, un hombre de origen catalán le es impedido ejercer su oficio de panadero, limitándolo a la producción de pastelería fina. La decisión fue tomada por el comandante del fuerte ante un pedido de un grupo de panaderas que se consideraban 'patricias', señalando el origen español de dicho panadero para limitarlo en el ejercicio del oficio. El conflicto nos ofrece varias aristas interesantes sobre los mecanismos del ejercicio del poder que estamos viendo en otros trabajos, pero aquí nos detendremos en la definición del grupo de pertenencia y en la utilización de los conceptos de patria y patriotas
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La obra vincula las instituciones, el orden público y la construcción de una ciudadanía en la Pampa Central con la extensión de propiedades de construcción del Estado que el gobierno federal intentaba concretar en los territorios nacionales -fines del siglo XIX-. Se analizan las instituciones, su constitución, funcionamiento e inconvenientes. Se reconstruyen las relaciones de la incipiente sociedad civil que estaba adquiriendo rasgos de "ciudadanía", pese a la limitación del derecho a la soberanía y representación política, por cuya razón se abocó al reducido poder local, a la conversión del Territorio en provincia y a la presión sobre las instituciones del Estado. Ciertos sectores sociales -vecinos propietarios- participaron en el poder y pudieron incidir en la disposición de un determinado orden público. Se descubre este entramado a través de la cuestión política, la constitución de la esfera pública, el papel de la prensa, y el accionar de sectores gubernamentales y particulares, especialmente en los conflictos sociales. Estas cuestiones se analizan con mayor profundidad en el estudio particular de una institución: la justicia letrada nacional con marcado poder en el Territorio. Se demuestra que esta institución ejerció un papel importante en la extensión de las propiedades que caracterizaron la construcción y consolidación del Estado. El protagonismo judicial a nivel nacional tuvo su correlación en el poder de los jueces y de los juzgados letrados territoriales, basado en: el carácter nacional de estos tribunales, el perfil profesional de sus miembros, una red social y política de los magistrados a nivel nacional y, la debilidad de las demás instituciones del Territorio. Este poder era reconocido y consolidado por la prensa y los vecinos -propietarios, comerciantes y profesionales- interesados en jerarquizar el papel de la justicia.
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Este artículo se propone analizar la forma en que se implantó la Justicia de Paz en el interior de la provincia de Buenos Aires entre 1865 y 1910, a través del estudio de los sujetos que desempeñaron esa función y los entramados políticos en los que participaron. El mismo se ha realizado a partir del estudio de un Juzgado en particular, como fue el del partido de Tres Arroyos. Por un lado, se reconstruye el perfil de los sujetos que ejercieron el cargo de Jueces de Paz, con la intención de entender las lógicas que guiaron su designación. Para ello, se indaga en la reconstrucción de sus biografías asociadas a los diversos momentos de ocupación e institucionalización local. Posteriormente se identifican dos modos de nucleamiento que sirvieron de base relacional a los individuos del lugar y que permiten completar la explicación generada desde las biografías individuales: una red de tipo iniciática, como fue la masonería; y una red del conservadurismo local, dirigida por poderosos estancieros del lugar. Por último, se observa si esas redes influyeron en la administración de justicia local. Las fuentes utilizadas son diversos álbumes conmemorativos locales, datos censales, periódicos locales, expedientes correccionales tramitados en la Justicia de Paz de Tres Arroyos, el Libro Copiador de Notas del Juzgado y el Libro de Actas de la Logia Hiram de Tres Arroyos.
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Se evalúa con indicadores de gobernanza urbana la sostenibilidad de las formas de hacer ciudad hibrida compleja del gobierno de la gestión visible (GGV). Argumenta que el GGV hace ciudad para legitimarse por desempeño y fortalecer la gobernanza local, en un contexto de mutaciones múltiples y radicales que tienden a diluir y centralizar el poder local y fractalizar la ciudad, profundizando la segregación sociopolítica-territorial y la ingobernabilidad genética de la ciudad hibrida, poniendo en riesgo el Estado federal descentralizado, el derecho a la ciudad, al gobierno local y la gobernanza urbana y multinivel (hipótesis). La estrategia de evaluación de gobernanza innovadora (EEG+i) diseñada para evaluar la relación entre las formas de hacer ciudad hibrida (variables espaciales) y gobernanza (variable a-espacial) es transversal, multidimensional y se construye desde la complejidad, el análisis de escenarios, formulación de constructos, modelos e indicadores de gobernanza, entretejiendo tres campos de conocimiento, gobierno, ciudad y sostenibilidad, en cuatro fases. La Fase 1, contextualiza la gobernanza en la dramática del siglo XXI. La Fase 2, desarrolla la fundamentación teórico-práctica, nuevos conceptos y un abordaje analítico propio ‘genética territorial’, para analizar y comprehender la complejidad de la ciudad hibrida de países en desarrollo, tejiendo ontogenética territorial y el carácter autopoiético del gen informal. En la Fase 3, se caracterizan las formas de hacer ciudad desde la genética del territorio, se formulan modelos e indicadores de gobernanza con los que se evalúan, aplicando un delphi y cuestionarios, los genes tipológicos-formas de hacer ciudad y validan las conclusiones. En la Fase 4, se correlacionan los resultados de los instrumentos aplicados con la praxis urbana del GGV, durante cuatro periodos de gobierno (1996-2010). Concluyendo que, la estrategia de evaluación comprobó las hipótesis y demostró la correlación transversal y multinivel existente entre, las mutaciones en curso que contradicen el modelo de gobernanza constitucional, el paisaje de gobernanza latinoamericano y venezolano, la praxis de los regímenes híbridos ricos en recursos naturales, las perspectivas de desarrollo globales y se expresa sociopolíticamente en déficit de gobernanza, Estado de derecho y cohesión-capital social y, espaciolocalmente, en la ciudad hibrida dispersa y diluida (compleja) y en el gobierno del poder diluido centralizado. La confrontación de flujos de poder centrípetos y centrífugos en la ciudad profundiza la fragmentación socioespacial y política y el deterioro de la calidad de vida, incrementando las protestas ciudadanas e ingobernabilidad que obstaculiza la superación de la pobreza y gobernanza urbana y multinivel. La evaluación de la praxis urbana del GGV evidenció que la correlación entre gobernanza, la producción de genes formales y la ciudad por iniciativa privada tiende a ser positiva y entre gobernanza, genes y producción de ciudad informal negativa, por el carácter autopoiético-autogobernable del gen informal y de los nuevos gobiernos sublocales que dificulta gobernar en gobernanza. La praxis del GGV es contraria al modelo de gobernanza formulado y la disolución centralizada del gobierno local y de la ciudad hibrida-dispersa es socio-espacial y políticamente insostenible. Se proponen estrategias y tácticas de gobernanza multinivel para recuperar la cohesión social y de planificación de la gestión innovadora (EG [PG] +i) para orquestar, desde el Consejo Local de Gobernanza (CLG) y con la participación de los espacios y gobiernos sublocales, un proyecto de ciudad compartido y sostenible. ABSTRACT The sustainability of the forms of making the hybrid-complex city by the visible management government (VMG) is evaluated using urban governance indicators. Argues that the VMG builds city to legitimate itself by performance and to strengthen local governance in a context of multiple and radical mutations that tend to dilute and centralize local power and fractalize the city, deepening the socio-spatial and political segregation, the genetic ingovernability of the hybrid city and placing the decentralized federal State, the right to city, local government and urban governance at risk (hypothesis). The innovative governance evaluation strategy (GES+i) designed to assess the relationship between the forms of making the hybrid city (spatial variables) and governance (a-spatial variable) is transversal, multidimensional; is constructed from complexity, scenario analysis, the formulation of concepts, models and governance indicators, weaving three fields of knowledge, government, city and sustainability in four phases. Phase 1, contextualizes governance in the dramatic of the twenty-first century. Phase 2, develops the theoretical and practical foundations, new concepts and a proper analytical approach to comprehend the complexity of the hybrid city from developing countries, weaving territorial ontogenetic with the autopiethic character of the informal city gen. In Phase 3, the ways of making city are characterized from the genetics of territory; governance indicators and models are formulated to evaluate, using delphi and questionnaires, the ways of making city and validate the conclusions. In Phase 4, the results of the instruments applied are correlated with the urban praxis of the VMG during the four periods of government analyzed (1996-2010). Concluding that, the evaluation strategy proved the hypothesis and showed the transversal and multilevel correlation between, mutations that contradict the constitutional governance model, the governance landscape of Latinamerica and the country, the praxis of the hybrid regimes rich in natural resources, the perspectives of the glocal economy and expresses socio-politically the governance and rule of law and social capital-cohesion deficit and spatial-temporarily the hybrid disperse and diluted city (complex) and the diluted-centralized local government. The confrontation of flows of power centripetal and centrifugal in the city deepens the socio-spatial and political fragmentation and deterioration of the quality of life, increasing citizens' protests and ingovernability which hinders poverty eradication and, multilevel and urban governance. The evaluation of the VMG urban praxis showed the correlation between governance, the production of formal genes and city by private initiative tended to be positive and, between informal genes-city production and governance negative, due to its autopiethic-self governable character that hinders governance. The urban praxis of the VMG contradicts the formulated governance model and thecentralized dissolution of the local government and hybrid city are socio-spatial and politically unsustainable. Multiscale governance strategies are proposed to recreate social cohesion and a management planning innovative method (EG [PG] + i) to orchestrate, from the Local Governance Council (LGC) and with the participation of sublocal governments and spaces, a shared and sustainable city project.
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Electricity price forecasting is an interesting problem for all the agents involved in electricity market operation. For instance, every profit maximisation strategy is based on the computation of accurate one-day-ahead forecasts, which is why electricity price forecasting has been a growing field of research in recent years. In addition, the increasing concern about environmental issues has led to a high penetration of renewable energies, particularly wind. In some European countries such as Spain, Germany and Denmark, renewable energy is having a deep impact on the local power markets. In this paper, we propose an optimal model from the perspective of forecasting accuracy, and it consists of a combination of several univariate and multivariate time series methods that account for the amount of energy produced with clean energies, particularly wind and hydro, which are the most relevant renewable energy sources in the Iberian Market. This market is used to illustrate the proposed methodology, as it is one of those markets in which wind power production is more relevant in terms of its percentage of the total demand, but of course our method can be applied to any other liberalised power market. As far as our contribution is concerned, first, the methodology proposed by García-Martos et al(2007 and 2012) is generalised twofold: we allow the incorporation of wind power production and hydro reservoirs, and we do not impose the restriction of using the same model for 24h. A computational experiment and a Design of Experiments (DOE) are performed for this purpose. Then, for those hours in which there are two or more models without statistically significant differences in terms of their forecasting accuracy, a combination of forecasts is proposed by weighting the best models(according to the DOE) and minimising the Mean Absolute Percentage Error (MAPE). The MAPE is the most popular accuracy metric for comparing electricity price forecasting models. We construct the combi nation of forecasts by solving several nonlinear optimisation problems that allow computation of the optimal weights for building the combination of forecasts. The results are obtained by a large computational experiment that entails calculating out-of-sample forecasts for every hour in every day in the period from January 2007 to Decem ber 2009. In addition, to reinforce the value of our methodology, we compare our results with those that appear in recent published works in the field. This comparison shows the superiority of our methodology in terms of forecasting accuracy.
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A Iluminação Pública (IP) está num momento de profundas mudanças, principalmente com a popularização da tecnologia LED e dos sistemas de controle a distância. O gestor de serviços públicos precisa conhecer a complexidade do uso final da IP para que possa gerir esse ativo direcionado às necessidades dos usuários, tendo em vista o dinamismo de evolução diária dos centros urbanos. Este estudo tem por objetivo desenvolver uma metodologia que permite levantar, cadastrar, diagnosticar e avaliar, o parque de IP existente em ambientes urbanos. Tem como questão de pesquisa: Como prover os gestores de serviços públicos de conhecimento da situação dos ativos de IP? Trata-se de uma pesquisa observacional e descritiva, desenvolvida em uma região que compreende uma área de 26,5 km², com uma população de 344.632 habitantes, localizada em uma região metropolitana brasileira. A metodologia aplicada divide-se em dois momentos: pesquisa documental e de campo. Inicia-se com um levantamento de documentações a respeito da vida pregressa do acervo, disponíveis nos escritórios da Concessionária de Energia local e da Prefeitura Municipal. Posteriormente procede-se uma identificação do perfil da cidade, onde o sistema de iluminação está inserido, buscando compreender como o sistema de IP instalado está integrado às necessidades da população. Essas primeiras ações visam recolher subsídios para a etapa seguinte, de levantamento técnico em campo, que buscou identificar não só os atributos de IP existentes para atualização cadastral, como também identificou anomalias que estavam atrapalhando o desempenho do sistema e a influência provocada pelo meio onde está inserido. A metodologia pode ser uma ferramenta que contribui para a gestão do serviço de IP inserida dentro dos centros urbanos, possibilitando a adoção de medidas de ajustes que visem dotar o acervo de IP de uma estrutura de manutenção direcionada para cada região da cidade, considerando sua especificidade e perfil dos usuários. Antes de qualquer adoção de novas tecnologias, como por exemplo lâmpadas LED, telecomando, etc., é imprescindível que se tenha um diagnóstico do acervo existente e a identificação do uso final da IP no meio em que se encontra.
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Tese de mestrado integrado em Engenharia da Energia e do Ambiente, apresentada à Universidade de Lisboa, através da Faculdade de Ciências, 2016
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In recent months Kyiv has been intensifying its efforts to diversify Ukraine’s gas supply routes with a view to reducing the country’s dependence on imports from Russia. One of the steps which Kyiv has taken has been to make the unprecedented decision to start importing gas from its Western neighbours. In November 2012, Ukraine’s state-owned Naftogaz began importing gas through Poland under a two-month contract with RWE (the imports continued into 2013 under a separate deal), while in the spring of 2013 Ukraine started importing gas from Hungary. Kyiv is also currently looking into the possibility of purchasing gas from Slovakia. Furthermore, since 2010 the Ukrainian government has been working on the construction of an LNG terminal near Odesa. The authorities have declared that this will allow Ukraine to import up to 5 billion m3 of LNG a year by 2015. The government has also taken measures to increase domestic production, including from non-traditional sources, and it plans to replace gas-based with coal-based technologies in local power stations. Finally, in January 2013, the government signed a 50-year production sharing agreement with Shell. This paves the way for the development of Ukraine’s shale gas deposits.
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This paper explores alterations in social dynamics caused by coca crops in Curvaradó and Jiguamiandó, at Choco department in the Colombian Pacific region. The research analyzes the role of armed actors such as paramilitaries and guerrillas in the conformation of new social spaces where local people find resistance as the main tool to survive in chaotic environments. Local power as a politics of resistance is also analyzed. Non-governmental organizations are a key tool to comprehend new social configurations. By doing the analysis and comparison using political ecology as the theoretical background along with concepts of moral economy and everyday resistance, with qualitative research methods. The paper aims to interpret and provide a better understanding of those changes considering social-environmental relations. Findings suggest that those changes in social structure are leading to an understanding, not just of the organization of the area, but also that social dynamics and coca crops cannot be generalized in the country.
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The Front National has for some years been France's third political party and the most notable far-right force in Europe; its leader, Jean-Marie Le Pen, contested the 2002 presidential election run-off with 5.5 million votes. What do Le Pen and the FN represent? What are their historical roots, their values and their policies? Who votes for them and why? And what has been their impact on the political agenda in France? Adopting an essentially chronological approach, the book traces the political lineage of Le Pen and the FN through key figures, movements and events on the French extreme right from the Vichy regime to the present, providing a detailed historical perspective for understanding the FN today. Part I provides a historical study of the extreme right in France since 1940, examining • the Vichy regime, collaboration and ‘collaborationism’, • the aftermath of Liberation and the post-war extreme right, • the Poujadist movement and the politics of populism, • the Algerian War as a catalyst for change, • the ‘Nouvelle Droite’ and the search for doctrinal renewal, • old and new forms of extreme-right ideology and activism. Part II undertakes a comprehensive study of the FN, analysing • the party’s early development and electoral rise, • its evolving programme and strategy, • the factors underlying its popular appeal, • the geography and composition of its electorate, • its exercise of local power and regional influence, • and its defining impact on the national political agenda. The FN, it is argued, represents both the latest manifestation of a long tradition of authoritarian nationalism and a complex new phenomenon within the changing social and political dynamics of contemporary France.
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Large broadening of short optical pulses due to fiber dispersion leads to a strong overlap in information data streams resulting in statistical deviations of the local power from its average. We present a theoretical analysis of rare events of high-intensity fluctuations-optical freak waves-that occur in fiber communication links using bit-overlapping transmission. Although the nature of the large fluctuations examined here is completely linear, as compared to commonly studied freak waves generated by nonlinear effects, the considered deviations inherit from rogue waves the key features of practical interest-random appearance of localized high-intensity pulses. We use the term "rogue wave" in an unusual context mostly to attract attention to both the possibility of purely linear statistical generation of huge amplitude waves and to the fact that in optics the occurrence of such pulses might be observable even with the standard Gaussian or even rarer-than-Gaussian statistics, without imposing the condition of an increased probability of extreme value events. © 2011 American Physical Society.
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Statement of the problem. It seeks to examine whether structural adjustment in Jamaica produced the desired developmental effects for labor--both organized and non-unionized--and if there is any significant difference in the Dominican Republic, which did not undergo that economic transformation. The research hypothesis is; "Structural Adjustment leads to Marginalization of labor."^ Methodology used. The methodology is mostly a straight cross-sectional analysis using data sets and publications from the UN, ILO, World Bank and IDB, as well as local statistical sources. The dissertation is primarily an historical to contemporary analysis of the Jamaican experience under structural adjustment, as it related to labor. To a greater extent it involves a straight cross-national comparison on the historical experiences of each country and a discussion of the relative similarities and differences between them, and the impact these features had on labor.^ Summary of findings. In the end, the question is asked as to whether internal factors are important in the relative success or failure of development strategies. From the data there is some indication that under structural adjustment there has been limited economic benefits for labor in Jamaica while labor standards have not improved. In the Dominican Republic the economic performance has been similar but the labor standards have improved significantly. This thus leads to the conclusion that structural adjustment may have been a factor in the resistance to labor's empowerment.^ Nevertheless, the study also shows that there may have been a causal role which local power relations had. The suggestion from the study is that in analyzing the phenomenon, attention must be paid to internal as well as external dynamics and variables. ^
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Abstract
The goal of modern radiotherapy is to precisely deliver a prescribed radiation dose to delineated target volumes that contain a significant amount of tumor cells while sparing the surrounding healthy tissues/organs. Precise delineation of treatment and avoidance volumes is the key for the precision radiation therapy. In recent years, considerable clinical and research efforts have been devoted to integrate MRI into radiotherapy workflow motivated by the superior soft tissue contrast and functional imaging possibility. Dynamic contrast-enhanced MRI (DCE-MRI) is a noninvasive technique that measures properties of tissue microvasculature. Its sensitivity to radiation-induced vascular pharmacokinetic (PK) changes has been preliminary demonstrated. In spite of its great potential, two major challenges have limited DCE-MRI’s clinical application in radiotherapy assessment: the technical limitations of accurate DCE-MRI imaging implementation and the need of novel DCE-MRI data analysis methods for richer functional heterogeneity information.
This study aims at improving current DCE-MRI techniques and developing new DCE-MRI analysis methods for particular radiotherapy assessment. Thus, the study is naturally divided into two parts. The first part focuses on DCE-MRI temporal resolution as one of the key DCE-MRI technical factors, and some improvements regarding DCE-MRI temporal resolution are proposed; the second part explores the potential value of image heterogeneity analysis and multiple PK model combination for therapeutic response assessment, and several novel DCE-MRI data analysis methods are developed.
I. Improvement of DCE-MRI temporal resolution. First, the feasibility of improving DCE-MRI temporal resolution via image undersampling was studied. Specifically, a novel MR image iterative reconstruction algorithm was studied for DCE-MRI reconstruction. This algorithm was built on the recently developed compress sensing (CS) theory. By utilizing a limited k-space acquisition with shorter imaging time, images can be reconstructed in an iterative fashion under the regularization of a newly proposed total generalized variation (TGV) penalty term. In the retrospective study of brain radiosurgery patient DCE-MRI scans under IRB-approval, the clinically obtained image data was selected as reference data, and the simulated accelerated k-space acquisition was generated via undersampling the reference image full k-space with designed sampling grids. Two undersampling strategies were proposed: 1) a radial multi-ray grid with a special angular distribution was adopted to sample each slice of the full k-space; 2) a Cartesian random sampling grid series with spatiotemporal constraints from adjacent frames was adopted to sample the dynamic k-space series at a slice location. Two sets of PK parameters’ maps were generated from the undersampled data and from the fully-sampled data, respectively. Multiple quantitative measurements and statistical studies were performed to evaluate the accuracy of PK maps generated from the undersampled data in reference to the PK maps generated from the fully-sampled data. Results showed that at a simulated acceleration factor of four, PK maps could be faithfully calculated from the DCE images that were reconstructed using undersampled data, and no statistically significant differences were found between the regional PK mean values from undersampled and fully-sampled data sets. DCE-MRI acceleration using the investigated image reconstruction method has been suggested as feasible and promising.
Second, for high temporal resolution DCE-MRI, a new PK model fitting method was developed to solve PK parameters for better calculation accuracy and efficiency. This method is based on a derivative-based deformation of the commonly used Tofts PK model, which is presented as an integrative expression. This method also includes an advanced Kolmogorov-Zurbenko (KZ) filter to remove the potential noise effect in data and solve the PK parameter as a linear problem in matrix format. In the computer simulation study, PK parameters representing typical intracranial values were selected as references to simulated DCE-MRI data for different temporal resolution and different data noise level. Results showed that at both high temporal resolutions (<1s) and clinically feasible temporal resolution (~5s), this new method was able to calculate PK parameters more accurate than the current calculation methods at clinically relevant noise levels; at high temporal resolutions, the calculation efficiency of this new method was superior to current methods in an order of 102. In a retrospective of clinical brain DCE-MRI scans, the PK maps derived from the proposed method were comparable with the results from current methods. Based on these results, it can be concluded that this new method can be used for accurate and efficient PK model fitting for high temporal resolution DCE-MRI.
II. Development of DCE-MRI analysis methods for therapeutic response assessment. This part aims at methodology developments in two approaches. The first one is to develop model-free analysis method for DCE-MRI functional heterogeneity evaluation. This approach is inspired by the rationale that radiotherapy-induced functional change could be heterogeneous across the treatment area. The first effort was spent on a translational investigation of classic fractal dimension theory for DCE-MRI therapeutic response assessment. In a small-animal anti-angiogenesis drug therapy experiment, the randomly assigned treatment/control groups received multiple fraction treatments with one pre-treatment and multiple post-treatment high spatiotemporal DCE-MRI scans. In the post-treatment scan two weeks after the start, the investigated Rényi dimensions of the classic PK rate constant map demonstrated significant differences between the treatment and the control groups; when Rényi dimensions were adopted for treatment/control group classification, the achieved accuracy was higher than the accuracy from using conventional PK parameter statistics. Following this pilot work, two novel texture analysis methods were proposed. First, a new technique called Gray Level Local Power Matrix (GLLPM) was developed. It intends to solve the lack of temporal information and poor calculation efficiency of the commonly used Gray Level Co-Occurrence Matrix (GLCOM) techniques. In the same small animal experiment, the dynamic curves of Haralick texture features derived from the GLLPM had an overall better performance than the corresponding curves derived from current GLCOM techniques in treatment/control separation and classification. The second developed method is dynamic Fractal Signature Dissimilarity (FSD) analysis. Inspired by the classic fractal dimension theory, this method measures the dynamics of tumor heterogeneity during the contrast agent uptake in a quantitative fashion on DCE images. In the small animal experiment mentioned before, the selected parameters from dynamic FSD analysis showed significant differences between treatment/control groups as early as after 1 treatment fraction; in contrast, metrics from conventional PK analysis showed significant differences only after 3 treatment fractions. When using dynamic FSD parameters, the treatment/control group classification after 1st treatment fraction was improved than using conventional PK statistics. These results suggest the promising application of this novel method for capturing early therapeutic response.
The second approach of developing novel DCE-MRI methods is to combine PK information from multiple PK models. Currently, the classic Tofts model or its alternative version has been widely adopted for DCE-MRI analysis as a gold-standard approach for therapeutic response assessment. Previously, a shutter-speed (SS) model was proposed to incorporate transcytolemmal water exchange effect into contrast agent concentration quantification. In spite of richer biological assumption, its application in therapeutic response assessment is limited. It might be intriguing to combine the information from the SS model and from the classic Tofts model to explore potential new biological information for treatment assessment. The feasibility of this idea was investigated in the same small animal experiment. The SS model was compared against the Tofts model for therapeutic response assessment using PK parameter regional mean value comparison. Based on the modeled transcytolemmal water exchange rate, a biological subvolume was proposed and was automatically identified using histogram analysis. Within the biological subvolume, the PK rate constant derived from the SS model were proved to be superior to the one from Tofts model in treatment/control separation and classification. Furthermore, novel biomarkers were designed to integrate PK rate constants from these two models. When being evaluated in the biological subvolume, this biomarker was able to reflect significant treatment/control difference in both post-treatment evaluation. These results confirm the potential value of SS model as well as its combination with Tofts model for therapeutic response assessment.
In summary, this study addressed two problems of DCE-MRI application in radiotherapy assessment. In the first part, a method of accelerating DCE-MRI acquisition for better temporal resolution was investigated, and a novel PK model fitting algorithm was proposed for high temporal resolution DCE-MRI. In the second part, two model-free texture analysis methods and a multiple-model analysis method were developed for DCE-MRI therapeutic response assessment. The presented works could benefit the future DCE-MRI routine clinical application in radiotherapy assessment.