Evaluación de la cobertura dosimétrica tumoral en tratamientos radioterápicos de cáncer de pulmón

El uso de técnicas radioterápicas basadas en la modulación de haces, supone un aumento de las divergencias dosimétricas encontradas entre los sistemas convencionales de planificación comercial y algoritmos de calculo más detallado, como el método Montecarlo, especialmente en situaciones de alta heterogeneidad de tejidos. Estas variaciones en los valores de dosis absorbida tienen una especial importancia en su distribución dosimétrica en el volumen tumoral, propiciando la posible aparición de zonas infradosificadas que conllevaría pérdidas en la probabilidad de control tumoral. Nuestro objetivo principal en este proyecto de tesis es conocer el origen de estas discrepancias dosimétricas entre sistemas de cálculo, y ahondar en las implicaciones clínicas que tienen lugar para casos clínicos de cáncer de pulmón. Para ello, utilizaremos el código geant4 como referencia de cálculo Montecarlo. Manteniendo como directriz principal la consecución del objetivo planteado, este trabajo se divide en tres partes: en primer lugar analizaremos a modo de introducción los aspectos más generales del cáncer de pulmón, comentando las técnicas de radioterapia utilizadas con mayor frecuencia para su tratamiento. Seguidamente se describen los elementos involucrados en el proceso de irradiación del paciente, i. e. el acelerador lineal de electrones y el sistema de planificación comercial. Junto a ello, exponemos una breve mención de la película radiocrómica como detector a emplear en la dosimetría. Finalmente, presentamos las propiedades más relevantes del método Montecarlo y del código geant4. En la segunda parte, evaluamos una serie de aplicaciones geant4 dirigidas hacia la validación dosimétrica del modelado de los elementos del cabezal del acelerador lineal Siemens Oncor Impression Plus, instalado en el Hospital Universitario Virgen Macarena (Sevilla, España), a través de la comparativa con medidas experimentales efectuadas con cámara de ionización en agua. Junto a ello, hemos constatado las diferencias entre distribuciones de dosis calculadas en geant4 y el sistema de planificación comercial, comparándolas con la medida con película radiocrómica en un maniquí antropomórfico. Éste incluye materiales de composición química y densidad física conocidas. Por tanto, los estudios definidos en este párrafo constituyen la sección académica de nuestro proyecto de tesis. Para la tercera y última parte, que definimos como la parte realista del proyecto de tesis, utilizamos imágenes DICOM para crear los modelos geométricos del maniquí y paciente a través de nuestras herramientas desarrolladas con el código geant4. De esta forma conseguimos que exista igualdad en términos geométricos entre el sistema de planificación y el método Montecarlo. En primer lugar, hemos analizado las divergencias dosimétricas para los cálculos, comparándolos con las medidas, en la geometría voxelizada del maniquí. Por último, hemos realizado el mismo proceso para tratamientos reales de cáncer de pulmón. En este caso hemos evaluado asimismo las consecuencias radiobiológicas, debidas a estas discrepancias dosimétricas encontradas, a través del cálculo de la probabilidad de control tumoral.The use of radiotherapy techniques based on beam modulation suposes an increment of dose divergences between treatment planning system and more sofisticated calculation algorithm, like Monte Carlo method, specially in situations of high hetereogeneity of tissues. These absorbed dose variations have a special importance on dose distribution at the tumoral volume, creating the possible presence of underdosed regions which implies lost in tumor control probability. Our main task in this thesis project is to know the origin of these dosimetric divergences between calculation systems, and go in deep with the clinical implications in lung cancer clinical cases. For this purpose, we are going to use geant4 as Monte Carlo calculation reference. Keeping the achievement of the aim as main guideline, this work is divided in three parts: first of all we are going to analyse the most general aspects of lung cancer as introduction, including the most frequent radiotherapy techniques for lung cancer treatment. Following we describe the items involved in patient irradiation process, i. e. the lineal accelerator and the treatment planning system. Moreover, we describe the radiochromic film as the detector to employ in dose measurements. Finally, we present the more relevant properties of the Monte Carlo method and geant4 code. On the second part we evaluate sereval geant4 applications developed towards dosimetric validation of the geometrical model of the items which compose the treatment head of the Siemens Oncor Impression Plus linac, installed at the Hospital Universitario Virgen Macarena (Seville, Spain), through the comparison between experimental measurements acquired with ionization chamber in water. Furthermore, we have taken into account the differences between dose distributions calculated with geant4 and the treatment planning system, making comparisons with experimental dose distribution measured with radiochromic film inserted inside a anthropomorfic phantom. This phantom includes several materials with known chemical compositions and physical densities. Hence, these studies defined above represent the academic section of our thesis project. Finally, on the third and last part we define the realistic component of the thesis project. We use DICOM images for developing the geometric models of the phantom and patient through our geant4 tools. In this way we achieve an equality in geometric terms between treatment planning system and Monte Carlo method. First of all, we have analysed the dosimetric differences for the calculations (compared with the experimental values) at the voxelized geometry of the phantom. Lastly we have done the same process for real lung cancer treatments. In this case we have evaluated too the radiobiological consecuences due to dosimetric divergences thanks to the tumor control probability calculation

Determination of uric acid in synthetic urine by using electrochemical surface oxidation enhanced Raman scattering

In this work, a new and easy methodology to determine uric acid in relevant samples using Raman spectroelectrochemistry is presented. The spectroelectrochemistry experiment is based on the in-situ formation of a suitable substrate that enables the enhancement of the Raman signal of an analyte during the oxidation stage of a silver electrode. This phenomenon is known as electrochemical surface oxidation enhanced Raman scattering (EC-SOERS) and has proved to be useful in quantitative analysis using disposable screen printed electrodes. The successful combination of EC-SOERS with PARAFAC analysis allows the determination of uric acid in a relevant complex sample avoiding the use of standard addition method and without using a baseline correction, which simplifies the application of such methodology in routine analysis.Ministerio de Economía y Competitividad (Grants CTQ2017-83935-R-AEI/FEDERUE) and Junta de Castilla y León (Grant BU297P18

Electrochemical SERS and SOERS in a single experiment: A new methodology for quantitative analysis

In the present work, a new methodology which combines two different phenomena to enhance the Raman signal is used to resolve a mixture of two compounds with similar molecular structures. The use of Raman spectroelectrochemistry (Raman-SEC) allows us to collect simultaneously, with high time-resolution, the enhancement of the Raman signal of the compounds present in a sample during the electrochemical oxidation-reduction cycle (ORC) of a silver screen-printed electrode. During such ORC two different phenomena appears depending on the stage of the electrochemical modification of the silver substrate, which are known as electrochemical surface enhanced Raman scattering (EC-SERS) and electrochemical surface oxidation enhanced Raman scattering (EC-SOERS). This work is a proof of concept that demonstrates the advantage of using EC-SOERS and EC-SERS in a single experiment to resolve mixtures of similar molecules such as vitamin B3, which components are nicotinic acid and nicotinamide. Although the interaction between analytes and substrates influence a univariate calibration, the trilinear character of Raman-SEC makes possible to deconvolve such interactions and provide a good calibration curve for both, nicotinic acid and nicotinamide.Ministerio de Economía y Competitividad (Grants CTQ2017-83935-R-AEI/FEDERUE), Junta de Castilla y León (Grant BU033-U16 and BU297P18) and Ministerio de Ciencia, Innovación y Universidades (RED2018-102412-T). J.V.P-R. thanks JCyL for his postdoctoral fellowship (Grant BU033-U16

Effect of chloride and pH on the electrochemical surface oxidation enhanced Raman scattering

In the present work, electrochemical surface oxidation enhanced Raman scattering (EC-SOERS) was studied using time resolved Raman spectroelectrochemistry. This multiresponse technique allows us to obtain dynamic information about the processes taking place during the electrochemical oxidation of a silver substrate. EC-SOERS is particularly found in specific electrolytic conditions, namely, HClO4 0.1 M + KCl 5·10−3 M, and has a clear dependence on chloride concentration and pH, being the optimum values between 5·10−3 M and 1·10−2 M for chloride and pH = 1. In light of the results of this study, the appearance of the phenomenon is related to the modification of the electrode surface, yielding Ag/AgCl cubes as plasmonic structures, and the stability of such structures at low pH values. The results presented in this work could shed more light into the intricate EC-SOERS phenomenon which can be summarized as the increase of the Raman signal for a Raman probe molecule exclusively during the electrochemical oxidation of silver electrodes.Ministerio de Economía y Competitividad (Grants CTQ2017-83935-R-AEI/FEDERUE) and Junta de Castilla y León (Grant BU033-U16). J.V.P-R. thanks JCyL for his postdoctoral fellowship (Grant BU033-U16

PUE attack detection in CWSNs using anomaly detection techniques

Cognitive wireless sensor network (CWSN) is a new paradigm, integrating cognitive features in traditional wireless sensor networks (WSNs) to mitigate important problems such as spectrum occupancy. Security in cognitive wireless sensor networks is an important problem since these kinds of networks manage critical applications and data. The specific constraints of WSN make the problem even more critical, and effective solutions have not yet been implemented. Primary user emulation (PUE) attack is the most studied specific attack deriving from new cognitive features. This work discusses a new approach, based on anomaly behavior detection and collaboration, to detect the primary user emulation attack in CWSN scenarios. Two non-parametric algorithms, suitable for low-resource networks like CWSNs, have been used in this work: the cumulative sum and data clustering algorithms. The comparison is based on some characteristics such as detection delay, learning time, scalability, resources, and scenario dependency. The algorithms have been tested using a cognitive simulator that provides important results in this area. Both algorithms have shown to be valid in order to detect PUE attacks, reaching a detection rate of 99% and less than 1% of false positives using collaboration

Controlling the degradation of wireless sensor networks

With the fast expansion of Wireless Sensor Networks (WSNs) and the increasing emergence of new scenarios and applications, extending their lifetime is crucial. Usually, WSN developers use generic algorithms and deployment arrangements without considering the specific needs of their network's application. Taking this application into account can result in a significant enhancement of performance, both in terms of increasing the lifetime and improving the quality of service (QoS). Furthermore, most WSN developers do not consider the final behavior of the network when nodes are nearly depleted and resources are scarce. In this paper we introduce the concept of the controlled degradation of the network, to refer to the strategies aimed at managing this deterioration process. The existing definitions of the network lifetime do not normally consider the specific purpose or application for which the WSN is intended. Thus, they are not suited to describe and test controlled degradation strategies. Consequently, we propose a new formal and comprehensive definition for the network lifetime. Finally, this work presents a proof of concept that confirms our statements and reinforces the potential of this research line

PUE attack detection in CWSN using collaboration and learning behavior

Cognitive Wireless Sensor Network (CWSN) is a new paradigm which integrates cognitive features in traditional Wireless Sensor Networks (WSNs) to mitigate important problems such as spectrum occupancy. Security in Cognitive Wireless Sensor Networks is an important problem because these kinds of networks manage critical applications and data. Moreover, the specific constraints of WSN make the problem even more critical. However, effective solutions have not been implemented yet. Among the specific attacks derived from new cognitive features, the one most studied is the Primary User Emulation (PUE) attack. This paper discusses a new approach, based on anomaly behavior detection and collaboration, to detect the PUE attack in CWSN scenarios. A nonparametric CUSUM algorithm, suitable for low resource networks like CWSN, has been used in this work. The algorithm has been tested using a cognitive simulator that brings important results in this area. For example, the result shows that the number of collaborative nodes is the most important parameter in order to improve the PUE attack detection rates. If the 20% of the nodes collaborates, the PUE detection reaches the 98% with less than 1% of false positives

Evaluation, energy optimization, and spectrum analysis of an artificial noise technique to improve CWSN security

This paper presents the security evaluation, energy consumption optimization, and spectrum scarcity analysis of artificial noise techniques to increase physical-layer security in Cognitive Wireless Sensor Networks (CWSNs). These techniques introduce noise into the spectrum in order to hide real information. Nevertheless, they directly affect two important parameters in Cognitive Wireless Sensor Networks (CWSNs), energy consumption and spectrum utilization. Both are affected because the number of packets transmitted by the network and the active period of the nodes increase. Security evaluation demonstrates that these techniques are effective against eavesdropper attacks, but also optimization allows for the implementation of these approaches in low-resource networks such as Cognitive Wireless Sensor Networks. In this work, the scenario is formally modeled and the optimization according to the simulation results and the impact analysis over the frequency spectrum are presented

A game theory based strategy for reducing energy consumption in cognitive WSN

Wireless sensor networks (WSNs) are one of the most important users of wireless communication technologies in the coming years and some challenges in this area must be addressed for their complete development. Energy consumption and spectrum availability are two of the most severe constraints of WSNs due to their intrinsic nature. The introduction of cognitive capabilities into these networks has arisen to face the issue of spectrum scarcity but could be used to face energy challenges too due to their new range of communication possibilities. In this paper a new strategy based on game theory for cognitive WSNs is discussed. The presented strategy improves energy consumption by taking advantage of the new change-communication-channel capability. Based on game theory, the strategy decides when to change the transmission channel depending on the behavior of the rest of the network nodes. The strategy presented is lightweight but still has higher energy saving rates as compared to noncognitive networks and even to other strategies based on scheduled spectrum sensing. Simulations are presented for several scenarios that demonstrate energy saving rates of around 65% as compared to WSNs without cognitive techniques

Amarguras y la reinvención literaria de Sevilla

La Sevilla que reinventaron los arquitectos del regionalismo hizo realidad la literatura, la leyenda, el tópico y la idealización de la ciudad dentro de un proceso de asombrosa convergencia creativa entre arquitectura, pintura, música, literatura y fiestas tradicionales. A la vez que edificaban González, Traver, Talavera o Espiau componía Joaquín Turina, escribían José María Izquierdo, José Más, Cansinos Assens, Chaves Nogales o Romero Murube, pintaban Bacarisas, García Ramos, Rico Cejudo o Juan Miguel Sánchez, estrenaban sus comedias los Álvarez Quintero y Muñoz Seca o componían Font de Anta y Farfán sus marchas para una Semana Santa en gran parte reinventada por Rodríguez Ojeda. Muchos procesos explican esta reinvención literaria, festiva o arquitectónica de Sevilla. Pero sobre todo el definido por el historiador Eric Hobsbawm como “invención de la tradición”, a través del que las colectividades que se han visto sometidas a las profundas y rápidas transformaciones de la modernidad buscaban seguridades, anclajes, continuidades, referencias, sentido de pertenencia, modificando sus antiguas tradiciones (caso sevillano de la Semana Santa a partir de la segunda mitad del XIX y sobre todo de las tres primeras décadas del siglo XX), o inventando nuevas tradiciones (caso de la Feria)