MASCG: Multi-Atlas Segmentation Constrained Graph method for accurate segmentation of hip CT images

This paper addresses the issue of fully automatic segmentation of a hip CT image with the goal to preserve the joint structure for clinical applications in hip disease diagnosis and treatment. For this purpose, we propose a Multi-Atlas Segmentation Constrained Graph (MASCG) method. The MASCG method uses multi-atlas based mesh fusion results to initialize a bone sheetness based multi-label graph cut for an accurate hip CT segmentation which has the inherent advantage of automatic separation of the pelvic region from the bilateral proximal femoral regions. We then introduce a graph cut constrained graph search algorithm to further improve the segmentation accuracy around the bilateral hip joint regions. Taking manual segmentation as the ground truth, we evaluated the present approach on 30 hip CT images (60 hips) with a 15-fold cross validation. When the present approach was compared to manual segmentation, an average surface distance error of 0.30 mm, 0.29 mm, and 0.30 mm was found for the pelvis, the left proximal femur, and the right proximal femur, respectively. A further look at the bilateral hip joint regions demonstrated an average surface distance error of 0.16 mm, 0.21 mm and 0.20 mm for the acetabulum, the left femoral head, and the right femoral head, respectively.

TIME SERIES ANALYSIS AS INPUT FOR PREDICTIVE MODELING: PREDICTING CARDIAC ARREST IN A PEDIATRIC INTENSIVE CARE UNIT

The first manuscript, entitled "Time-Series Analysis as Input for Clinical Predictive Modeling: Modeling Cardiac Arrest in a Pediatric ICU" lays out the theoretical background for the project. There are several core concepts presented in this paper. First, traditional multivariate models (where each variable is represented by only one value) provide single point-in-time snapshots of patient status: they are incapable of characterizing deterioration. Since deterioration is consistently identified as a precursor to cardiac arrests, we maintain that the traditional multivariate paradigm is insufficient for predicting arrests. We identify time series analysis as a method capable of characterizing deterioration in an objective, mathematical fashion, and describe how to build a general foundation for predictive modeling using time series analysis results as latent variables. Building a solid foundation for any given modeling task involves addressing a number of issues during the design phase. These include selecting the proper candidate features on which to base the model, and selecting the most appropriate tool to measure them. We also identified several unique design issues that are introduced when time series data elements are added to the set of candidate features. One such issue is in defining the duration and resolution of time series elements required to sufficiently characterize the time series phenomena being considered as candidate features for the predictive model. Once the duration and resolution are established, there must also be explicit mathematical or statistical operations that produce the time series analysis result to be used as a latent candidate feature. In synthesizing the comprehensive framework for building a predictive model based on time series data elements, we identified at least four classes of data that can be used in the model design. The first two classes are shared with traditional multivariate models: multivariate data and clinical latent features. Multivariate data is represented by the standard one value per variable paradigm and is widely employed in a host of clinical models and tools. These are often represented by a number present in a given cell of a table. Clinical latent features derived, rather than directly measured, data elements that more accurately represent a particular clinical phenomenon than any of the directly measured data elements in isolation. The second two classes are unique to the time series data elements. The first of these is the raw data elements. These are represented by multiple values per variable, and constitute the measured observations that are typically available to end users when they review time series data. These are often represented as dots on a graph. The final class of data results from performing time series analysis. This class of data represents the fundamental concept on which our hypothesis is based. The specific statistical or mathematical operations are up to the modeler to determine, but we generally recommend that a variety of analyses be performed in order to maximize the likelihood that a representation of the time series data elements is produced that is able to distinguish between two or more classes of outcomes. The second manuscript, entitled "Building Clinical Prediction Models Using Time Series Data: Modeling Cardiac Arrest in a Pediatric ICU" provides a detailed description, start to finish, of the methods required to prepare the data, build, and validate a predictive model that uses the time series data elements determined in the first paper. One of the fundamental tenets of the second paper is that manual implementations of time series based models are unfeasible due to the relatively large number of data elements and the complexity of preprocessing that must occur before data can be presented to the model. Each of the seventeen steps is analyzed from the perspective of how it may be automated, when necessary. We identify the general objectives and available strategies of each of the steps, and we present our rationale for choosing a specific strategy for each step in the case of predicting cardiac arrest in a pediatric intensive care unit. Another issue brought to light by the second paper is that the individual steps required to use time series data for predictive modeling are more numerous and more complex than those used for modeling with traditional multivariate data. Even after complexities attributable to the design phase (addressed in our first paper) have been accounted for, the management and manipulation of the time series elements (the preprocessing steps in particular) are issues that are not present in a traditional multivariate modeling paradigm. In our methods, we present the issues that arise from the time series data elements: defining a reference time; imputing and reducing time series data in order to conform to a predefined structure that was specified during the design phase; and normalizing variable families rather than individual variable instances. The final manuscript, entitled: "Using Time-Series Analysis to Predict Cardiac Arrest in a Pediatric Intensive Care Unit" presents the results that were obtained by applying the theoretical construct and its associated methods (detailed in the first two papers) to the case of cardiac arrest prediction in a pediatric intensive care unit. Our results showed that utilizing the trend analysis from the time series data elements reduced the number of classification errors by 73%. The area under the Receiver Operating Characteristic curve increased from a baseline of 87% to 98% by including the trend analysis. In addition to the performance measures, we were also able to demonstrate that adding raw time series data elements without their associated trend analyses improved classification accuracy as compared to the baseline multivariate model, but diminished classification accuracy as compared to when just the trend analysis features were added (ie, without adding the raw time series data elements). We believe this phenomenon was largely attributable to overfitting, which is known to increase as the ratio of candidate features to class examples rises. Furthermore, although we employed several feature reduction strategies to counteract the overfitting problem, they failed to improve the performance beyond that which was achieved by exclusion of the raw time series elements. Finally, our data demonstrated that pulse oximetry and systolic blood pressure readings tend to start diminishing about 10-20 minutes before an arrest, whereas heart rates tend to diminish rapidly less than 5 minutes before an arrest.

Alarm tree analysis using statistical techniques

This work presents a systematic method for the generation and treatment of the alarms' graphs, being its final object to find the Alarm Root Cause of the Massive Alarms that are produced in the dispatching centers. Although many works about this matter have been already developed, the problem about the alarm management in the industry is still completely unsolved. In this paper, a simple statistic analysis of the historical data base is conducted. The results obtained by the acquisition alarm systems, are used to generate a directed graph from which the more significant alarms are extracted, previously analyzing any possible case in which a great quantity of alarms are produced.

An investigation of the performance of a new Mechanical thrombectomy device using Bond Graph modelling: application to the extraction of blood clots in the middle cerebral artery

A number of thrombectomy devices using a variety of methods have now been developed to facilitate clot removal. We present research involving one such experimental device recently developed in the UK, called a ‘GP’ Thrombus Aspiration Device (GPTAD). This device has the potential to bring about the extraction of a thrombus. Although the device is at a relatively early stage of development, the results look encouraging. In this work, we present an analysis and modeling of the GPTAD by means of the bond graph technique; it seems to be a highly effective method of simulating the device under a variety of conditions. Such modeling is useful in optimizing the GPTAD and predicting the result of clot extraction. The aim of this simulation model is to obtain the minimum pressure necessary to extract the clot and to verify that both the pressure and the time required to complete the clot extraction are realistic for use in clinical situations, and are consistent with any experimentally obtained data. We therefore consider aspects of rheology and mechanics in our modeling.

A graph-based approach for latency modeling and optimization in multiview video encoding

We present a novel framework for encoding latency analysis of arbitrary multiview video coding prediction structures. This framework avoids the need to consider an specific encoder architecture for encoding latency analysis by assuming an unlimited processing capacity on the multiview encoder. Under this assumption, only the influence of the prediction structure and the processing times have to be considered, and the encoding latency is solved systematically by means of a graph model. The results obtained with this model are valid for a multiview encoder with sufficient processing capacity and serve as a lower bound otherwise. Furthermore, with the objective of low latency encoder design with low penalty on rate-distortion performance, the graph model allows us to identify the prediction relationships that add higher encoding latency to the encoder. Experimental results for JMVM prediction structures illustrate how low latency prediction structures with a low rate-distortion penalty can be derived in a systematic manner using the new model.

A flexible (C)LP-based approach to the analysis of object-oriented programs

Static analyses of object-oriented programs usually rely on intermediate representations that respect the original semantics while having a more uniform and basic syntax. Most of the work involving object-oriented languages and abstract interpretation usually omits the description of that language or just refers to the Control Flow Graph(CFG) it represents. However, this lack of formalization on one hand results in an absence of assurances regarding the correctness of the transformation and on the other it typically strongly couples the analysis to the source language. In this work we present a framework for analysis of object-oriented languages in which in a first phase we transform the input program into a representation based on Horn clauses. This allows on one hand proving the transformation correct attending to a simple condition and on the other being able to apply an existing analyzer for (constraint) logic programming to automatically derive a safe approximation of the semantics of the original program. The approach is flexible in the sense that the first phase decouples the analyzer from most languagedependent features, and correct because the set of Horn clauses returned by the transformation phase safely approximates the standard semantics of the input program. The resulting analysis is also reasonably scalable due to the use of mature, modular (C)LP-based analyzers. The overall approach allows us to report results for medium-sized programs.

A generic framework for the analysis and specialization of kogic programs

The relationship between abstract interpretation [2] and partial evaluation [5] has received considerable attention and (partial) integrations have been proposed starting from both the partial deduction (see e.g. [6] and its references) and abstract interpretation perspectives. Abstract interpretation-based analyzers (such as the CiaoPP analyzer [9,4]) generally compute a program analysis graph [1] in order to propagate (abstract) call and success information by performing fixpoint computations when needed. On the other hand, partial deduction methods [7] incorporate powerful techniques for on-line specialization including (concrete) call propagation and unfolding.

A generic framework for the analysis and specialization of logic programs

The relationship between abstract interpretation and partial deduction has received considerable attention and (partial) integrations have been proposed starting from both the partial deduction and abstract interpretation perspectives. In this work we present what we argüe is the first fully described generic algorithm for efñcient and precise integration of abstract interpretation and partial deduction. Taking as starting point state-of-the-art algorithms for context-sensitive, polyvariant abstract interpretation and (abstract) partial deduction, we present an algorithm which combines the best of both worlds. Key ingredients include the accurate success propagation inherent to abstract interpretation and the powerful program transformations achievable by partial deduction. In our algorithm, the calis which appear in the analysis graph are not analyzed w.r.t. the original definition of the procedure but w.r.t. specialized definitions of these procedures. Such specialized definitions are obtained by applying both unfolding and abstract executability. Our framework is parametric w.r.t. different control strategies and abstract domains. Different combinations of such parameters correspond to existing algorithms for program analysis and specialization. Simultaneously, our approach opens the door to the efñcient computation of strictly more precise results than those achievable by each of the individual techniques. The algorithm is now one of the key components of the CiaoPP analysis and specialization system.

A generic, context sensitive analysis framework for object oriented programs

Abstract interpreters rely on the existence of a nxpoint algorithm that calculates a least upper bound approximation of the semantics of the program. Usually, that algorithm is described in terms of the particular language in study and therefore it is not directly applicable to programs written in a different source language. In this paper we introduce a generic, block-based, and uniform representation of the program control flow graph and a language-independent nxpoint algorithm that can be applied to a variety of languages and, in particular, Java. Two major characteristics of our approach are accuracy (obtained through a topdown, context sensitive approach) and reasonable efficiency (achieved by means of memoization and dependency tracking techniques). We have also implemented the proposed framework and show some initial experimental results for standard benchmarks, which further support the feasibility of the solution adopted.

A framework for the analysis and optimization of delay in multiview video coding schemes

Esta tesis presenta un novedoso marco de referencia para el análisis y optimización del retardo de codificación y descodificación para vídeo multivista. El objetivo de este marco de referencia es proporcionar una metodología sistemática para el análisis del retardo en codificadores y descodificadores multivista y herramientas útiles en el diseño de codificadores/descodificadores para aplicaciones con requisitos de bajo retardo. El marco de referencia propuesto caracteriza primero los elementos que tienen influencia en el comportamiento del retardo: i) la estructura de predicción multivista, ii) el modelo hardware del codificador/descodificador y iii) los tiempos de proceso de cuadro. En segundo lugar, proporciona algoritmos para el cálculo del retardo de codificación/ descodificación de cualquier estructura arbitraria de predicción multivista. El núcleo de este marco de referencia consiste en una metodología para el análisis del retardo de codificación/descodificación multivista que es independiente de la arquitectura hardware del codificador/descodificador, completada con un conjunto de modelos que particularizan este análisis del retardo con las características de la arquitectura hardware del codificador/descodificador. Entre estos modelos, aquellos basados en teoría de grafos adquieren especial relevancia debido a su capacidad de desacoplar la influencia de los diferentes elementos en el comportamiento del retardo en el codificador/ descodificador, mediante una abstracción de su capacidad de proceso. Para revelar las posibles aplicaciones de este marco de referencia, esta tesis presenta algunos ejemplos de su utilización en problemas de diseño que afectan a codificadores y descodificadores multivista. Este escenario de aplicación cubre los siguientes casos: estrategias para el diseño de estructuras de predicción que tengan en consideración requisitos de retardo además del comportamiento tasa-distorsión; diseño del número de procesadores y análisis de los requisitos de velocidad de proceso en codificadores/ descodificadores multivista dado un retardo objetivo; y el análisis comparativo del comportamiento del retardo en codificadores multivista con diferentes capacidades de proceso e implementaciones hardware. ABSTRACT This thesis presents a novel framework for the analysis and optimization of the encoding and decoding delay for multiview video. The objective of this framework is to provide a systematic methodology for the analysis of the delay in multiview encoders and decoders and useful tools in the design of multiview encoders/decoders for applications with low delay requirements. The proposed framework characterizes firstly the elements that have an influence in the delay performance: i) the multiview prediction structure ii) the hardware model of the encoder/decoder and iii) frame processing times. Secondly, it provides algorithms for the computation of the encoding/decoding delay of any arbitrary multiview prediction structure. The core of this framework consists in a methodology for the analysis of the multiview encoding/decoding delay that is independent of the hardware architecture of the encoder/decoder, which is completed with a set of models that particularize this delay analysis with the characteristics of the hardware architecture of the encoder/decoder. Among these models, the ones based in graph theory acquire special relevance due to their capacity to detach the influence of the different elements in the delay performance of the encoder/decoder, by means of an abstraction of its processing capacity. To reveal possible applications of this framework, this thesis presents some examples of its utilization in design problems that affect multiview encoders and decoders. This application scenario covers the following cases: strategies for the design of prediction structures that take into consideration delay requirements in addition to the rate-distortion performance; design of number of processors and analysis of processor speed requirements in multiview encoders/decoders given a target delay; and comparative analysis of the encoding delay performance of multiview encoders with different processing capabilities and hardware implementations.

A framework for the analysis and optimization of encoding latency for multiview video

We present a novel framework for the analysis and optimization of encoding latency for multiview video. Firstly, we characterize the elements that have an influence in the encoding latency performance: (i) the multiview prediction structure and (ii) the hardware encoder model. Then, we provide algorithms to find the encoding latency of any arbitrary multiview prediction structure. The proposed framework relies on the directed acyclic graph encoder latency (DAGEL) model, which provides an abstraction of the processing capacity of the encoder by considering an unbounded number of processors. Using graph theoretic algorithms, the DAGEL model allows us to compute the encoding latency of a given prediction structure, and determine the contribution of the prediction dependencies to it. As an example of DAGEL application, we propose an algorithm to reduce the encoding latency of a given multiview prediction structure up to a target value. In our approach, a minimum number of frame dependencies are pruned, until the latency target value is achieved, thus minimizing the degradation of the rate-distortion performance due to the removal of the prediction dependencies. Finally, we analyze the latency performance of the DAGEL derived prediction structures in multiview encoders with limited processing capacity.

Self-organizing cultured neural networks: Image analysis techniques for longitudinal tracking and modeling of the underlying network structure

Esta tesis estudia la evolución estructural de conjuntos de neuronas como la capacidad de auto-organización desde conjuntos de neuronas separadas hasta que forman una red (clusterizada) compleja. Esta tesis contribuye con el diseño e implementación de un algoritmo no supervisado de segmentación basado en grafos con un coste computacional muy bajo. Este algoritmo proporciona de forma automática la estructura completa de la red a partir de imágenes de cultivos neuronales tomadas con microscopios de fase con una resolución muy alta. La estructura de la red es representada mediante un objeto matemático (matriz) cuyos nodos representan a las neuronas o grupos de neuronas y los enlaces son las conexiones reconstruidas entre ellos. Este algoritmo extrae también otras medidas morfológicas importantes que caracterizan a las neuronas y a las neuritas. A diferencia de otros algoritmos hasta el momento, que necesitan de fluorescencia y técnicas inmunocitoquímicas, el algoritmo propuesto permite el estudio longitudinal de forma no invasiva posibilitando el estudio durante la formación de un cultivo. Además, esta tesis, estudia de forma sistemática un grupo de variables topológicas que garantizan la posibilidad de cuantificar e investigar la progresión de las características principales durante el proceso de auto-organización del cultivo. Nuestros resultados muestran la existencia de un estado concreto correspondiente a redes con configuracin small-world y la emergencia de propiedades a micro- y meso-escala de la estructura de la red. Finalmente, identificamos los procesos físicos principales que guían las transformaciones morfológicas de los cultivos y proponemos un modelo de crecimiento de red que reproduce el comportamiento cuantitativamente de las observaciones experimentales. ABSTRACT The thesis analyzes the morphological evolution of assemblies of living neurons, as they self-organize from collections of separated cells into elaborated, clustered, networks. In particular, it contributes with the design and implementation of a graph-based unsupervised segmentation algorithm, having an associated very low computational cost. The processing automatically retrieves the whole network structure from large scale phase-contrast images taken at high resolution throughout the entire life of a cultured neuronal network. The network structure is represented by a mathematical object (a matrix) in which nodes are identified neurons or neurons clusters, and links are the reconstructed connections between them. The algorithm is also able to extract any other relevant morphological information characterizing neurons and neurites. More importantly, and at variance with other segmentation methods that require fluorescence imaging from immunocyto- chemistry techniques, our measures are non invasive and entitle us to carry out a fully longitudinal analysis during the maturation of a single culture. In turn, a systematic statistical analysis of a group of topological observables grants us the possibility of quantifying and tracking the progression of the main networks characteristics during the self-organization process of the culture. Our results point to the existence of a particular state corresponding to a small-world network configuration, in which several relevant graphs micro- and meso-scale properties emerge. Finally, we identify the main physical processes taking place during the cultures morphological transformations, and embed them into a simplified growth model that quantitatively reproduces the overall set of experimental observations.

Self-organizing cultured neural networks: Image analysis techniques for longitudinal tracking and modeling of the underlying network structure (versión actualizada)

Esta tesis estudia la evolución estructural de conjuntos de neuronas como la capacidad de auto-organización desde conjuntos de neuronas separadas hasta que forman una red (clusterizada) compleja. Esta tesis contribuye con el diseño e implementación de un algoritmo no supervisado de segmentación basado en grafos con un coste computacional muy bajo. Este algoritmo proporciona de forma automática la estructura completa de la red a partir de imágenes de cultivos neuronales tomadas con microscopios de fase con una resolución muy alta. La estructura de la red es representada mediante un objeto matemático (matriz) cuyos nodos representan a las neuronas o grupos de neuronas y los enlaces son las conexiones reconstruidas entre ellos. Este algoritmo extrae también otras medidas morfológicas importantes que caracterizan a las neuronas y a las neuritas. A diferencia de otros algoritmos hasta el momento, que necesitan de fluorescencia y técnicas inmunocitoquímicas, el algoritmo propuesto permite el estudio longitudinal de forma no invasiva posibilitando el estudio durante la formación de un cultivo. Además, esta tesis, estudia de forma sistemática un grupo de variables topológicas que garantizan la posibilidad de cuantificar e investigar la progresión de las características principales durante el proceso de auto-organización del cultivo. Nuestros resultados muestran la existencia de un estado concreto correspondiente a redes con configuracin small-world y la emergencia de propiedades a micro- y meso-escala de la estructura de la red. Finalmente, identificamos los procesos físicos principales que guían las transformaciones morfológicas de los cultivos y proponemos un modelo de crecimiento de red que reproduce el comportamiento cuantitativamente de las observaciones experimentales. ABSTRACT The thesis analyzes the morphological evolution of assemblies of living neurons, as they self-organize from collections of separated cells into elaborated, clustered, networks. In particular, it contributes with the design and implementation of a graph-based unsupervised segmentation algorithm, having an associated very low computational cost. The processing automatically retrieves the whole network structure from large scale phase-contrast images taken at high resolution throughout the entire life of a cultured neuronal network. The network structure is represented by a mathematical object (a matrix) in which nodes are identified neurons or neurons clusters, and links are the reconstructed connections between them. The algorithm is also able to extract any other relevant morphological information characterizing neurons and neurites. More importantly, and at variance with other segmentation methods that require fluorescence imaging from immunocyto- chemistry techniques, our measures are non invasive and entitle us to carry out a fully longitudinal analysis during the maturation of a single culture. In turn, a systematic statistical analysis of a group of topological observables grants us the possibility of quantifying and tracking the progression of the main networks characteristics during the self-organization process of the culture. Our results point to the existence of a particular state corresponding to a small-world network configuration, in which several relevant graphs micro- and meso-scale properties emerge. Finally, we identify the main physical processes taking place during the cultures morphological transformations, and embed them into a simplified growth model that quantitatively reproduces the overall set of experimental observations.

Mathematical foundations for efficient structural controllability and observability analysis of complex systems

The relationship between structural controllability and observability of complex systems is studied. Algebraic and graph theoretic tools are combined to prove the extent of some controller/observer duality results. Two types of control design problems are addressed and some fundamental theoretical results are provided. In addition new algorithms are presented to compute optimal solutions for monitoring large scale real networks.

Systematic analysis of the decoding delay in multiview video

We present a framework for the analysis of the decoding delay in multiview video coding (MVC). We show that in real-time applications, an accurate estimation of the decoding delay is essential to achieve a minimum communication latency. As opposed to single-view codecs, the complexity of the multiview prediction structure and the parallel decoding of several views requires a systematic analysis of this decoding delay, which we solve using graph theory and a model of the decoder hardware architecture. Our framework assumes a decoder implementation in general purpose multi-core processors with multi-threading capabilities. For this hardware model, we show that frame processing times depend on the computational load of the decoder and we provide an iterative algorithm to compute jointly frame processing times and decoding delay. Finally, we show that decoding delay analysis can be applied to design decoders with the objective of minimizing the communication latency of the MVC system.