Generación de modelos físicos personalizados y segmentación de la pared arterial y el trombo intraluminal en imágenes de aneurismas aórticos abdominales

Esta tesis doctoral está encuadrada dentro del marco general de la ingeniería biomédica aplicada al tratamiento de las enfermedades cardiovasculares, enfermedades que provocan alrededor de 1.9 millones (40%) de muertes al año en la Unión Europea. En este contexto surge el proyecto europeo SCATh-Smart Catheterization, cuyo objetivo principal es mejorar los procedimientos de cateterismo aórtico introduciendo nuevas tecnologías de planificación y navegación quirúrgica y minimizando el uso de fluoroscopía. En particular, esta tesis aborda el modelado y diagnóstico de aneurismas aórticos abdominales (AAA) y del trombo intraluminal (TIL), allí donde esté presente, así como la segmentación de estas estructuras en imágenes preoperatorias de RM. Los modelos físicos específicos del paciente, construidos a partir de imágenes médicas preoperatorias, tienen múltiples usos, que van desde la evaluación preoperatoria de estructuras anatómicas a la planificación quirúrgica para el guiado de catéteres. En el diagnóstico y tratamiento de AAA, los modelos físicos son útiles a la hora de evaluar diversas variables biomecánicas y fisiológicas de las estructuras vasculares. Existen múltiples técnicas que requieren de la generación de modelos físicos que representen la anatomía vascular. Una de las principales aplicaciones de los modelos físicos es el análisis de elementos finitos (FE). Las simulaciones de FE para AAA pueden ser específicas para el paciente y permiten modelar estados de estrés complejos, incluyendo los efectos provocados por el TIL. La aplicación de métodos numéricos de análisis tiene como requisito previo la generación de una malla computacional que representa la geometría de interés mediante un conjunto de elementos poliédricos, siendo los hexaédricos los que presentan mejores resultados. En las estructuras vasculares, generar mallas hexaédricas es un proceso especialmente exigente debido a la compleja anatomía 3D ramificada. La mayoría de los AAA se encuentran situados en la bifurcación de la arteria aorta en las arterias iliacas y es necesario modelar de manera fiel dicha bifurcación. En el caso de que la sangre se estanque en el aneurisma provocando un TIL, éste forma una estructura adyacente a la pared aórtica. De este modo, el contorno externo del TIL es el mismo que el contorno interno de la pared, por lo que las mallas resultantes deben reflejar esta particularidad, lo que se denomina como "mallas conformadas". El fin último de este trabajo es modelar las estructuras vasculares de modo que proporcionen nuevas herramientas para un mejor diagnóstico clínico, facilitando medidas de riesgo de rotura de la arteria, presión sistólica o diastólica, etc. Por tanto, el primer objetivo de esta tesis es diseñar un método novedoso y robusto para generar mallas hexaédricas tanto de la pared aórtica como del trombo. Para la identificación de estas estructuras se utilizan imágenes de resonancia magnética (RM). Deben mantenerse sus propiedades de adyacencia utilizando elementos de alta calidad, prestando especial atención al modelado de la bifurcación y a que sean adecuadas para el análisis de FE. El método tiene en cuenta la evolución de la línea central del vaso en el espacio tridimensional y genera la malla directamente a partir de las imágenes segmentadas, sin necesidad de reconstruir superficies triangulares. Con el fin de reducir la intervención del usuario en el proceso de generación de las mallas, es también objetivo de esta tesis desarrollar un método de segmentación semiautomática de las distintas estructuras de interés. Las principales contribuciones de esta tesis doctoral son: 1. El diseño, implementación y evaluación de un algoritmo de generación de mallas hexaédricas conformadas de la pared y el TIL a partir de los contornos segmentados en imágenes de RM. Se ha llevado a cabo una evaluación de calidad que determine su aplicabilidad a métodos de FE. Los resultados demuestran que el algoritmo desarrollado genera mallas conformadas de alta calidad incluso en la región de la bifurcación, que son adecuadas para su uso en métodos de análisis de FE. 2. El diseño, implementación y evaluación de un método de segmentación automático de las estructuras de interés. La luz arterial se segmenta de manera semiautomática utilizando un software disponible a partir de imágenes de RM con contraste. Los resultados de este proceso sirven de inicialización para la segmentación automática de las caras interna y externa de la pared aórtica utilizando métodos basado en modelos de textura y forma a partir de imágenes de RM sin contraste. Los resultados demuestran que el algoritmo desarrollado proporciona segmentaciones fieles de las distintas estructuras de interés. En conclusión, el trabajo realizado en esta tesis doctoral corrobora las hipótesis de investigación postuladas, y pretende servir como aportación para futuros avances en la generación de modelos físicos de geometrías biológicas. ABSTRACT The frame of this PhD Thesis is the biomedical engineering applied to the treatment of cardiovascular diseases, which cause around 1.9 million deaths per year in the European Union and suppose about 40% of deaths per year. In this context appears the European project SCATh-Smart Catheterization. The main objective of this project is creating a platform which improves the navigation of catheters in aortic catheterization minimizing the use of fluoroscopy. In the framework of this project, the specific field of this PhD Thesis is the diagnosis and modeling of abdominal aortic aneurysm (AAAs) and the intraluminal thrombus (ILT) whenever it is present. Patient-specific physical models built from preoperative imaging are becoming increasingly important in the area of minimally invasive surgery. These models can be employed for different purposes, such as the preoperatory evaluation of anatomic structures or the surgical planning for catheter guidance. In the specific case of AAA diagnosis and treatment, physical models are especially useful for evaluating pressures over vascular structures. There are multiple techniques that require the generation of physical models which represent the target anatomy. Finite element (FE) analysis is one the principal applications for physical models. FE simulations for AAA may be patient-specific and allow modeling biomechanical and physiological variables including those produced by ILT, and also the segmentation of those anatomical structures in preoperative MR images. Applying numeric methods requires the generation of a proper computational mesh. These meshes represent the patient anatomy using a set of polyhedral elements, with hexahedral elements providing better results. In the specific case of vascular structures, generating hexahedral meshes is a challenging task due to the complex 3D branching anatomy. Each patient’s aneurysm is unique, characterized by its location and shape, and must be accurately represented for subsequent analyses to be meaningful. Most AAAs are located in the region where the aorta bifurcates into the iliac arteries and it is necessary to model this bifurcation precisely and reliably. If blood stagnates in the aneurysm and forms an ILT, it exists as a conforming structure with the aortic wall, i.e. the ILT’s outer contour is the same as the wall’s inner contour. Therefore, resulting meshes must also be conforming. The main objective of this PhD Thesis is designing a novel and robust method for generating conforming hexahedral meshes for the aortic wall and the thrombus. These meshes are built using largely high-quality elements, especially at the bifurcation, that are suitable for FE analysis of tissue stresses. The method accounts for the evolution of the vessel’s centerline which may develop outside a single plane, and generates the mesh directly from segmented images without the requirement to reconstruct triangular surfaces. In order to reduce the user intervention in the mesh generation process is also a goal of this PhD. Thesis to develop a semiautomatic segmentation method for the structures of interest. The segmentation is performed from magnetic resonance image (MRI) sequences that have tuned to provide high contrast for the arterial tissue against the surrounding soft tissue, so that we determine the required information reliably. The main contributions of this PhD Thesis are: 1. The design, implementation and evaluation of an algorithm for generating hexahedral conforming meshes of the arterial wall and the ILT from the segmented contours. A quality inspection has been applied to the meshes in order to determine their suitability for FE methods. Results show that the developed algorithm generates high quality conforming hexahedral meshes even at the bifurcation region. Thus, these meshes are suitable for FE analysis. 2. The design, implementation and evaluation of a semiautomatic segmentation method for the structures of interest. The lumen is segmented in a semiautomatic way from contrast filled MRI using an available software. The results obtained from this process are used to initialize the automatic segmentation of the internal and external faces of the aortic wall. These segmentations are performed by methods based on texture and shape models from MRI with no contrast. The results show that the algorithm provides faithful segmentations of the structures of interest requiring minimal user intervention. In conclusion, the work undertaken in this PhD. Thesis verifies the investigation hypotheses. It intends to serve as basis for future physical model generation of proper biological anatomies used by numerical methods.

Biomechanical evaluation of the singing voice

Teaching the adequate use of the singing voice conveys a lot of knowledge in musical performance as well as in objective estimation techniques involving the use of air, muscles, room and body acoustics, and the tuning of a fine instrument as the human voice. Although subjective evaluation and training is a very delicate task to be carried out only by expert singers, biomedical engineering may help contributing with well-funded methodologies developed for the study of voice pathology. The present work is a preliminary study of exploratory character describing the performance of a student singer in a regular classroom under the point of view of vocal fold biomechanics. Estimates of biomechanical parameters obtained from singing voice are given and their potential use is discussed.

Vocal fold biomechanical analysis for the singing voice

Teaching the adequate use of the singing voice conveys a lot of knowledge in musical performance as well as in objective estimation techniques involving the use of air, muscles, room and body acoustics, and the tuning of a fine instrument as the human voice. Although subjective evaluation and training is a very delicate task to be carried out only by expert singers, biomedical engineering may help contributing with well - funded methodologies developed for the study of voice pathology. The present study is a preliminary study of exploratory character describing the performance of a student singer in a regular classroom under the point of view of vocal fold biomechanics. Estimate s of biomechanical parameters obtained from singing voice are given and their use i n the classroom is discussed.

Construcción automática de grafos RDF a partir de frases en lenguaje natural para la integración de bases de datos heterogéneas

El presente trabajo desarrolla un servicio REST que transforma frases en lenguaje natural a grafos RDF. Los grafos generados son grafos dirigidos, donde los nodos se forman con los sustantivos o adjetivos de las frases, y los arcos se forman con los verbos. Se utiliza dentro del proyecto p-medicine para dar soporte a las siguientes funcionalidades: Búsquedas en lenguaje natural: actualmente la plataforma p-medicine proporciona un interfaz programático para realizar consultas en SPARQL. El servicio desarrollado permitiría generar esas consultas automáticamente a partir de frases en lenguaje natural. Anotaciones de bases de datos mediante lenguaje natural: la plataforma pmedicine incorpora una herramienta, desarrollada por el Grupo de Ingeniería Biomédica de la Universidad Politécnica de Madrid, para la anotación de bases de datos RDF. Estas anotaciones son necesarias para la posterior traducción de las bases de datos a un esquema central. El proceso de anotación requiere que el usuario construya de forma manual las vistas RDF que desea anotar, lo que requiere mostrar gráficamente el esquema RDF y que el usuario construya vistas RDF seleccionando las clases y relaciones necesarias. Este proceso es a menudo complejo y demasiado difícil para un usuario sin perfil técnico. El sistema se incorporará para permitir que la construcción de estas vistas se realice con lenguaje natural. ---ABSTRACT---The present work develops a REST service that transforms natural language sentences to RDF degrees. Generated graphs are directed graphs where nodes are formed with nouns or adjectives of phrases, and the arcs are formed with verbs. Used within the p-medicine project to support the following functionality: Natural language queries: currently the p-medicine platform provides a programmatic interface to query SPARQL. The developed service would automatically generate those queries from natural language sentences. Memos databases using natural language: the p-medicine platform incorporates a tool, developed by the Group of Biomedical Engineering at the Polytechnic University of Madrid, for the annotation of RDF data bases. Such annotations are necessary for the subsequent translation of databases to a central scheme. The annotation process requires the user to manually construct the RDF views that he wants annotate, requiring graphically display the RDF schema and the user to build RDF views by selecting classes and relationships. This process is often complex and too difficult for a user with no technical background. The system is incorporated to allow the construction of these views to be performed with natural language.

A supervised cooperative learning system for early detection of language disorders

The Quality of Life of a person may depend on early attention to his neurodevel-opment disorders in childhood. Identification of language disorders under the age of six years old can speed up required diagnosis and/or treatment processes. This paper details the enhancement of a Clinical Decision Support System (CDSS) aimed to assist pediatricians and language therapists at early identification and re-ferral of language disorders. The system helps to fine tune the Knowledge Base of Language Delays (KBLD) that was already developed and validated in clinical routine with 146 children. Medical experts supported the construction of Gades CDSS by getting scientific consensus from literature and fifteen years of regis-tered use cases of children with language disorders. The current research focuses on an innovative cooperative model that allows the evolution of the KBLD of Gades through the supervised evaluation of the CDSS learnings with experts¿ feedback. The deployment of the resulting system is being assessed under a mul-tidisciplinary team of seven experts from the fields of speech therapist, neonatol-ogy, pediatrics, and neurology.

Predicting EQ-5D from the Parkinson's disease questionnaire PDQ-8 using multi-dimensional Bayesian network classifiers

The impact of the Parkinson's disease and its treatment on the patients' health-related quality of life can be estimated either by means of generic measures such as the european quality of Life-5 Dimensions (EQ-5D) or specific measures such as the 8-item Parkinson's disease questionnaire (PDQ-8). In clinical studies, PDQ-8 could be used in detriment of EQ-5D due to the lack of resources, time or clinical interest in generic measures. Nevertheless, PDQ-8 cannot be applied in cost-effectiveness analyses which require generic measures and quantitative utility scores, such as EQ-5D. To deal with this problem, a commonly used solution is the prediction of EQ-5D from PDQ-8. In this paper, we propose a new probabilistic method to predict EQ-5D from PDQ-8 using multi-dimensional Bayesian network classifiers. Our approach is evaluated using five-fold cross-validation experiments carried out on a Parkinson's data set containing 488 patients, and is compared with two additional Bayesian network-based approaches, two commonly used mapping methods namely, ordinary least squares and censored least absolute deviations, and a deterministic model. Experimental results are promising in terms of predictive performance as well as the identification of dependence relationships among EQ-5D and PDQ-8 items that the mapping approaches are unable to detect

Análisis espectral de señales cardiacas mediante frecuencia dominante

La Ingeniería Biomédica surgió en la década de 1950 como una fascinante mezcla interdisciplinaria, en la cual la ingeniería, la biología y la medicina aunaban esfuerzos para analizar y comprender distintas enfermedades. Las señales existentes en este área deben ser analizadas e interpretadas, más allá de las capacidades limitadas de la simple vista y la experiencia humana. Aquí es donde el procesamiento digital de la señal se postula como una herramienta indispensable para extraer la información relevante oculta en dichas señales. La electrocardiografía fue una de las primeras áreas en las que se aplicó el procesado digital de señales hace más de 50 años. Las señales electrocardiográficas continúan siendo, a día de hoy, objeto de estudio por parte de cardiólogos e ingenieros. En esta área, las técnicas de procesamiento de señal han ayudado a encontrar información oculta a simple vista que ha cambiado la forma de tratar ciertas enfermedades que fueron ya diagnosticadas previamente. Desde entonces, se han desarrollado numerosas técnicas de procesado de señales electrocardiográficas, pudiéndose resumir estas en tres grandes categorías: análisis tiempo-frecuencia, análisis de organización espacio-temporal y separación de la actividad atrial del ruido y las interferencias. Este proyecto se enmarca dentro de la primera categoría, análisis tiempo-frecuencia, y en concreto dentro de lo que se conoce como análisis de frecuencia dominante, la cual se va a aplicar al análisis de señales de fibrilación auricular. El proyecto incluye una parte teórica de análisis y desarrollo de algoritmos de procesado de señal, y una parte práctica, de programación y simulación con Matlab. Matlab es una de las herramientas fundamentales para el procesamiento digital de señales por ordenador, la cual presenta importantes funciones y utilidades para el desarrollo de proyectos en este campo. Por ello, se ha elegido dicho software como herramienta para la implementación del proyecto. ABSTRACT. Biomedical Engineering emerged in the 1950s as a fascinating interdisciplinary blend, in which engineering, biology and medicine pooled efforts to analyze and understand different diseases. Existing signals in this area should be analyzed and interpreted, beyond the limited capabilities of the naked eye and the human experience. This is where the digital signal processing is postulated as an indispensable tool to extract the relevant information hidden in these signals. Electrocardiography was one of the first areas where digital signal processing was applied over 50 years ago. Electrocardiographic signals remain, even today, the subject of close study by cardiologists and engineers. In this area, signal processing techniques have helped to find hidden information that has changed the way of treating certain diseases that were already previously diagnosed. Since then, numerous techniques have been developed for processing electrocardiographic signals. These methods can be summarized into three categories: time-frequency analysis, analysis of spatio-temporal organization and separation of atrial activity from noise and interferences. This project belongs to the first category, time-frequency analysis, and specifically to what is known as dominant frequency analysis, which is one of the fundamental tools applied in the analysis of atrial fibrillation signals. The project includes a theoretical part, related to the analysis and development of signal processing algorithms, and a practical part, related to programming and simulation using Matlab. Matlab is one of the fundamental tools for digital signal processing, presenting significant functions and advantages for the development of projects in this field. Therefore, we have chosen this software as a tool for project implementation.

Fluid-solid interaction in arteries incorporating the autoregulation concept in boundary conditions

In pre-surgery decisions in hospital emergency cases, fast and reliable results of the solid and fluid mechanics problems are of great interest to clinicians. In the current investigation, an iterative process based on a pressure-type boundary condition is proposed in order to reduce the computational costs of blood flow simulations in arteries, without losing control of the important clinical parameters. The incorporation of cardiovascular autoregulation, together with the well-known impedance boundary condition, forms the basis of the proposed methodology. With autoregulation, the instabilities associated with conventional pressure-type or impedance boundary conditions are avoided without an excessive increase in computational costs. The general behaviour of pulsatile blood flow in arteries, which is important from the clinical point of view, is well reproduced through this new methodology. In addition, the interaction between the blood and the arterial walls occurs via a modified weak coupling, which makes the simulation more stable and computationally efficient. Based on in vitro experiments, the hyperelastic behaviour of the wall is characterised and modelled. The applications and benefits of the proposed pressure-type boundary condition are shown in a model of an idealised aortic arch with and without an ascending aorta dissection, which is a common cardiovascular disorder.

A transient expansion of the native state precedes aggregation of recombinant human interferon-γ

Aggregation of proteins, even under conditions favoring the native state, is a ubiquitous problem in biotechnology and biomedical engineering. Providing a mechanistic basis for the pathways that lead to aggregation should allow development of rational approaches for its prevention. We have chosen recombinant human interferon-γ (rhIFN-γ) as a model protein for a mechanistic study of aggregation. In the presence of 0.9 M guanidinium hydrochloride, rhIFN-γ aggregates with first order kinetics, a process that is inhibited by addition of sucrose. We describe a pathway that accounts for both the observed first-order aggregation of rhIFN-γ and the effect of sucrose. In this pathway, aggregation proceeds through a transient expansion of the native state. Sucrose shifts the equilibrium within the ensemble of rhIFN-γ native conformations to favor the most compact native species over more expanded ones, thus stabilizing rhIFN-γ against aggregation. This phenomenon is attributed to the preferential exclusion of sucrose from the protein surface. In addition, kinetic analysis combined with solution thermodynamics shows that only a small (9%) expansion surface area is needed to form the transient native state that precedes aggregation. The approaches used here link thermodynamics and aggregation kinetics to provide a powerful tool for understanding both the pathway of protein aggregation and the rational use of excipients to inhibit the process.

DU05

http://digitalcommons.du.edu/natural_knee_data/1004/thumbnail.jpg

A high-resolution binocular video-oculography system: assessment of pupillary light reflex and detection of an early incomplete blink and an upward eye movement

Background: The pupillary light reflex characterizes the direct and consensual response of the eye to the perceived brightness of a stimulus. It has been used as indicator of both neurological and optic nerve pathologies. As with other eye reflexes, this reflex constitutes an almost instantaneous movement and is linked to activation of the same midbrain area. The latency of the pupillary light reflex is around 200 ms, although the literature also indicates that the fastest eye reflexes last 20 ms. Therefore, a system with sufficiently high spatial and temporal resolutions is required for accurate assessment. In this study, we analyzed the pupillary light reflex to determine whether any small discrepancy exists between the direct and consensual responses, and to ascertain whether any other eye reflex occurs before the pupillary light reflex. Methods: We constructed a binocular video-oculography system two high-speed cameras that simultaneously focused on both eyes. This was then employed to assess the direct and consensual responses of each eye using our own algorithm based on Circular Hough Transform to detect and track the pupil. Time parameters describing the pupillary light reflex were obtained from the radius time-variation. Eight healthy subjects (4 women, 4 men, aged 24–45) participated in this experiment. Results: Our system, which has a resolution of 15 microns and 4 ms, obtained time parameters describing the pupillary light reflex that were similar to those reported in previous studies, with no significant differences between direct and consensual reflexes. Moreover, it revealed an incomplete reflex blink and an upward eye movement at around 100 ms that may correspond to Bell’s phenomenon. Conclusions: Direct and consensual pupillary responses do not any significant temporal differences. The system and method described here could prove useful for further assessment of pupillary and blink reflexes. The resolution obtained revealed the existence reported here of an early incomplete blink and an upward eye movement.

Oil/water separation : state-of-the-art /

Mode of access: Internet.

A study of severe vehicular accidents. Phase 2.

National Highway Safety Bureau, Washington, D.C.

Polymerizable Peptide Monomers for the Targeted and Intracellular Delivery of Cancer Therapeutics

Thesis (Ph.D.)--University of Washington, 2016-06

Closed-Loop Deep Brain Stimulation: Bidirectional Neuroprosthetics for Tremor and BCI

Thesis (Ph.D.)--University of Washington, 2016-06