Rapid prototyping for biomedical engineering: current capabilities and Challenges

A new set of manufacturing technologies has emerged in the past decades to address market requirements in a customized way and to provide support for research tasks that require prototypes. These new techniques and technologies are usually referred to as rapid prototyping and manufacturing technologies, and they allow prototypes to be produced in a wide range of materials with remarkable precision in a couple of hours. Although they have been rapidly incorporated into product development methodologies, they are still under development, and their applications in bioengineering are continuously evolving. Rapid prototyping and manufacturing technologies can be of assistance in every stage of the development process of novel biodevices, to address various problems that can arise in the devices' interactions with biological systems and the fact that the design decisions must be tested carefully. This review focuses on the main fields of application for rapid prototyping in biomedical engineering and health sciences, as well as on the most remarkable challenges and research trends.

Identifying the semantics of eligibility criteria of clinical trials based on relevant medical ontologies

An important objective of the INTEGRATE project1 is to build tools that support the efficient execution of post-genomic multi-centric clinical trials in breast cancer, which includes the automatic assessment of the eligibility of patients for available trials. The population suited to be enrolled in a trial is described by a set of free-text eligibility criteria that are both syntactically and semantically complex. At the same time, the assessment of the eligibility of a patient for a trial requires the (machineprocessable) understanding of the semantics of the eligibility criteria in order to further evaluate if the patient data available for example in the hospital EHR satisfies these criteria. This paper presents an analysis of the semantics of the clinical trial eligibility criteria based on relevant medical ontologies in the clinical research domain: SNOMED-CT, LOINC, MedDRA. We detect subsets of these widely-adopted ontologies that characterize the semantics of the eligibility criteria of trials in various clinical domains and compare these sets. Next, we evaluate the occurrence frequency of the concepts in the concrete case of breast cancer (which is our first application domain) in order to provide meaningful priorities for the task of binding/mapping these ontology concepts to the actual patient data. We further assess the effort required to extend our approach to new domains in terms of additional semantic mappings that need to be developed.

Development of a Knowledge Base for smart screening of language disorders in primary care

Monitoring of neuro-evolutive development from birth until the age of six is a decisive factor in a child's quality of life. Early detection of development disorders in early childhood can facilitate necessary diagnosis and/or treatment. Primary-care pediatricians play a key role in early detection of development alterations as they can undertake the preventive and therapeutic actions necessary in the interest of a child's optimal development. The focus of this research paper is the construction of a Knowledge Base for smart screening aimed to assist pediatricians in processes of early referral in language disorders. The proposed model provides health professionals with a decision-making tool that supports referral processes. In this way, essential diagnostic and/or therapeutic actions are triggered for a comprehensive individual development. The resulting system was developed on the basis of an analysis and verification of 21 cases of children with language disorders.

Large scale multiphysics modeling of neurites

Situado en el límite entre Ingeniería, Informática y Biología, la mecánica computacional de las neuronas aparece como un nuevo campo interdisciplinar que potencialmente puede ser capaz de abordar problemas clínicos desde una perspectiva diferente. Este campo es multiescala por naturaleza, yendo desde la nanoescala (como, por ejemplo, los dímeros de tubulina) a la macroescala (como, por ejemplo, el tejido cerebral), y tiene como objetivo abordar problemas que son complejos, y algunas veces imposibles, de estudiar con medios experimentales. La modelización computacional ha sido ampliamente empleada en aplicaciones Neurocientíficas tan diversas como el crecimiento neuronal o la propagación de los potenciales de acción compuestos. Sin embargo, en la mayoría de los enfoques de modelización hechos hasta ahora, la interacción entre la célula y el medio/estímulo que la rodea ha sido muy poco explorada. A pesar de la tremenda importancia de esa relación en algunos desafíos médicos—como, por ejemplo, lesiones traumáticas en el cerebro, cáncer, la enfermedad del Alzheimer—un puente que relacione las propiedades electrofisiológicas-químicas y mecánicas desde la escala molecular al nivel celular todavía no existe. Con ese objetivo, esta investigación propone un marco computacional multiescala particularizado para dos escenarios respresentativos: el crecimiento del axón y el acomplamiento electrofisiológicomecánico de las neuritas. En el primer caso, se explora la relación entre los constituyentes moleculares del axón durante su crecimiento y sus propiedades mecánicas resultantes, mientras que en el último, un estímulo mecánico provoca deficiencias funcionales a nivel celular como consecuencia de sus alteraciones electrofisiológicas-químicas. La modelización computacional empleada en este trabajo es el método de las diferencias finitas, y es implementada en un nuevo programa llamado Neurite. Aunque el método de los elementos finitos es también explorado en parte de esta investigación, el método de las diferencias finitas tiene la flexibilidad y versatilidad necesaria para implementar mode los biológicos, así como la simplicidad matemática para extenderlos a simulaciones a gran escala con un coste computacional bajo. Centrándose primero en el efecto de las propiedades electrofisiológicas-químicas sobre las propiedades mecánicas, una versión adaptada de Neurite es desarrollada para simular la polimerización de los microtúbulos en el crecimiento del axón y proporcionar las propiedades mecánicas como función de la ocupación de los microtúbulos. Después de calibrar el modelo de crecimiento del axón frente a resultados experimentales disponibles en la literatura, las características mecánicas pueden ser evaluadas durante la simulación. Las propiedades mecánicas del axón muestran variaciones dramáticas en la punta de éste, donde el cono de crecimiento soporta las señales químicas y mecánicas. Bansándose en el conocimiento ganado con el modelo de diferencias finitas, y con el objetivo de ir de 1D a 3D, este esquema preliminar pero de una naturaleza innovadora allana el camino a futuros estudios con el método de los elementos finitos. Centrándose finalmente en el efecto de las propiedades mecánicas sobre las propiedades electrofisiológicas- químicas, Neurite es empleado para relacionar las cargas mecánicas macroscópicas con las deformaciones y velocidades de deformación a escala microscópica, y simular la propagación de la señal eléctrica en las neuritas bajo carga mecánica. Las simulaciones fueron calibradas con resultados experimentales publicados en la literatura, proporcionando, por tanto, un modelo capaz de predecir las alteraciones de las funciones electrofisiológicas neuronales bajo cargas externas dañinas, y uniendo lesiones mecánicas con las correspondientes deficiencias funcionales. Para abordar simulaciones a gran escala, aunque otras arquitecturas avanzadas basadas en muchos núcleos integrados (MICs) fueron consideradas, los solvers explícito e implícito se implementaron en unidades de procesamiento central (CPU) y unidades de procesamiento gráfico (GPUs). Estudios de escalabilidad fueron llevados acabo para ambas implementaciones mostrando resultados prometedores para casos de simulaciones extremadamente grandes con GPUs. Esta tesis abre la vía para futuros modelos mecánicos con el objetivo de unir las propiedades electrofisiológicas-químicas con las propiedades mecánicas. El objetivo general es mejorar el conocimiento de las comunidades médicas y de bioingeniería sobre la mecánica de las neuronas y las deficiencias funcionales que aparecen de los daños producidos por traumatismos mecánicos, como lesiones traumáticas en el cerebro, o enfermedades neurodegenerativas como la enfermedad del Alzheimer. ABSTRACT Sitting at the interface between Engineering, Computer Science and Biology, Computational Neuron Mechanics appears as a new interdisciplinary field potentially able to tackle clinical problems from a new perspective. This field is multiscale by nature, ranging from the nanoscale (e.g., tubulin dimers) to the macroscale (e.g., brain tissue), and aims at tackling problems that are complex, and sometime impossible, to study through experimental means. Computational modeling has been widely used in different Neuroscience applications as diverse as neuronal growth or compound action potential propagation. However, in the majority of the modeling approaches done in this field to date, the interactions between the cell and its surrounding media/stimulus have been rarely explored. Despite of the tremendous importance of such relationship in several medical challenges—e.g., traumatic brain injury (TBI), cancer, Alzheimer’s disease (AD)—a bridge between electrophysiological-chemical and mechanical properties of neurons from the molecular scale to the cell level is still lacking. To this end, this research proposes a multiscale computational framework particularized for two representative scenarios: axon growth and electrophysiological-mechanical coupling of neurites. In the former case, the relation between the molecular constituents of the axon during its growth and its resulting mechanical properties is explored, whereas in the latter, a mechanical stimulus provokes functional deficits at cell level as a consequence of its electrophysiological-chemical alterations. The computational modeling approach chosen in this work is the finite difference method (FDM), and was implemented in a new program called Neurite. Although the finite element method (FEM) is also explored as part of this research, the FDM provides the necessary flexibility and versatility to implement biological models, as well as the mathematical simplicity to extend them to large scale simulations with a low computational cost. Focusing first on the effect of electrophysiological-chemical properties on the mechanical proper ties, an adaptation of Neurite was developed to simulate microtubule polymerization in axonal growth and provide the axon mechanical properties as a function of microtubule occupancy. After calibrating the axon growth model against experimental results available in the literature, the mechanical characteristics can be tracked during the simulation. The axon mechanical properties show dramatic variations at the tip of the axon, where the growth cone supports the chemical and mechanical signaling. Based on the knowledge gained from the FDM scheme, and in order to go from 1D to 3D, this preliminary yet novel scheme paves the road for future studies with FEM. Focusing then on the effect of mechanical properties on the electrophysiological-chemical properties, Neurite was used to relate macroscopic mechanical loading to microscopic strains and strain rates, and simulate the electrical signal propagation along neurites under mechanical loading. The simulations were calibrated against experimental results published in the literature, thus providing a model able to predict the alteration of neuronal electrophysiological function under external damaging load, and linking mechanical injuries to subsequent acute functional deficits. To undertake large scale simulations, although other state-of-the-art architectures based on many integrated cores (MICs) were considered, the explicit and implicit solvers were implemented for central processing units (CPUs) and graphics processing units (GPUs). Scalability studies were done for both implementations showing promising results for extremely large scale simulations with GPUs. This thesis opens the avenue for future mechanical modeling approaches aimed at linking electrophysiological- chemical properties to mechanical properties. Its overarching goal is to enhance the bioengineering and medical communities knowledge on neuronal mechanics and functional deficits arising from damages produced by direct mechanical insults, such as TBI, or neurodegenerative evolving illness, such as AD.

Procesado de imágenes médicas en MATLAB

La relación entre la ingeniería y la medicina cada vez se está haciendo más estrecha, y debido a esto se ha creado una nueva disciplina, la bioingeniería, ámbito en el que se centra el proyecto. Este ámbito cobra gran interés debido al rápido desarrollo de nuevas tecnologías que en particular permiten, facilitan y mejoran la obtención de diagnósticos médicos respecto de los métodos tradicionales. Dentro de la bioingeniería, el campo que está teniendo mayor desarrollo es el de la imagen médica, gracias al cual se pueden obtener imágenes del interior del cuerpo humano con métodos no invasivos y sin necesidad de recurrir a la cirugía. Mediante métodos como la resonancia magnética, rayos X, medicina nuclear o ultrasonidos, se pueden obtener imágenes del cuerpo humano para realizar diagnósticos. Para que esas imágenes puedan ser utilizadas con ese fin hay que realizar un correcto tratamiento de éstas mediante técnicas de procesado digital. En ése ámbito del procesado digital de las imágenes médicas es en el que se ha realizado este proyecto. Gracias al desarrollo del tratamiento digital de imágenes con métodos de extracción de información, mejora de la visualización o resaltado de rasgos de interés de las imágenes, se puede facilitar y mejorar el diagnóstico de los especialistas. Por todo esto en una época en la que se quieren automatizar todos los procesos para mejorar la eficacia del trabajo realizado, el automatizar el procesado de las imágenes para extraer información con mayor facilidad, es muy útil. Actualmente una de las herramientas más potentes en el tratamiento de imágenes médicas es Matlab, gracias a su toolbox de procesado de imágenes. Por ello se eligió este software para el desarrollo de la parte práctica de este proyecto, su potencia y versatilidad simplifican la implementación de algoritmos. Este proyecto se estructura en dos partes. En la primera se realiza una descripción general de las diferentes modalidades de obtención de imágenes médicas y se explican los diferentes usos de cada método, dependiendo del campo de aplicación. Posteriormente se hace una descripción de las técnicas más importantes de procesado de imagen digital que han sido utilizadas en el proyecto. En la segunda parte se desarrollan cuatro aplicaciones en Matlab para ejemplificar el desarrollo de algoritmos de procesado de imágenes médicas. Dichas implementaciones demuestran la aplicación y utilidad de los conceptos explicados anteriormente en la parte teórica, como la segmentación y operaciones de filtrado espacial de la imagen, así como otros conceptos específicos. Las aplicaciones ejemplo desarrolladas han sido: obtención del porcentaje de metástasis de un tejido, diagnóstico de las deformidades de la columna vertebral, obtención de la MTF de una cámara de rayos gamma y medida del área de un fibroadenoma de una ecografía de mama. Por último, para cada una de las aplicaciones se detallará su utilidad en el campo de la imagen médica, los resultados obtenidos y su implementación en una interfaz gráfica para facilitar su uso. ABSTRACT. The relationship between medicine and engineering is becoming closer than ever giving birth to a recently appeared science field: bioengineering. This project is focused on this subject. This recent field is becoming more and more important due to the fast development of new technologies that provide tools to improve disease diagnosis, with regard to traditional procedures. In bioengineering the fastest growing field is medical imaging, in which we can obtain images of the inside of the human body without need of surgery. Nowadays by means of the medical modalities of magnetic resonance, X ray, nuclear medicine or ultrasound, we can obtain images to make a more accurate diagnosis. For those images to be useful within the medical field, they should be processed properly with some digital image processing techniques. It is in this field of digital medical image processing where this project is developed. Thanks to the development of digital image processing providing methods for data collection, improved visualization or data highlighting, diagnosis can be eased and facilitated. In an age where automation of processes is much sought, automated digital image processing to ease data collection is extremely useful. One of the most powerful image processing tools is Matlab, together with its image processing toolbox. That is the reason why that software was chosen to develop the practical algorithms in this project. This final project is divided into two main parts. Firstly, the different modalities for obtaining medical images will be described. The different usages of each method according to the application will also be specified. Afterwards we will give a brief description of the most important image processing tools that have been used in the project. Secondly, four algorithms in Matlab are implemented, to provide practical examples of medical image processing algorithms. This implementation shows the usefulness of the concepts previously explained in the first part, such as: segmentation or spatial filtering. The particular applications examples that have been developed are: calculation of the metastasis percentage of a tissue, diagnosis of spinal deformity, approximation to the MTF of a gamma camera, and measurement of the area of a fibroadenoma in an ultrasound image. Finally, for each of the applications developed, we will detail its usefulness within the medical field, the results obtained, and its implementation in a graphical user interface to ensure ease of use.

Analysis of the suitability of existing medical ontologies for building a scalable semantic interoperability solution supporting multi-site collaboration in oncology

Semantic interoperability is essential to facilitate efficient collaboration in heterogeneous multi-site healthcare environments. The deployment of a semantic interoperability solution has the potential to enable a wide range of informatics supported applications in clinical care and research both within as ingle healthcare organization and in a network of organizations. At the same time, building and deploying a semantic interoperability solution may require significant effort to carryout data transformation and to harmonize the semantics of the information in the different systems. Our approach to semantic interoperability leverages existing healthcare standards and ontologies, focusing first on specific clinical domains and key applications, and gradually expanding the solution when needed. An important objective of this work is to create a semantic link between clinical research and care environments to enable applications such as streamlining the execution of multi-centric clinical trials, including the identification of eligible patients for the trials. This paper presents an analysis of the suitability of several widely-used medical ontologies in the clinical domain: SNOMED-CT, LOINC, MedDRA, to capture the semantics of the clinical trial eligibility criteria, of the clinical trial data (e.g., Clinical Report Forms), and of the corresponding patient record data that would enable the automatic identification of eligible patients. Next to the coverage provided by the ontologies we evaluate and compare the sizes of the sets of relevant concepts and their relative frequency to estimate the cost of data transformation, of building the necessary semantic mappings, and of extending the solution to new domains. This analysis shows that our approach is both feasible and scalable.

Industriales Research Meeting 2016

Industriales Research Meeting 2016 (IRM16) is an event to show the research activities at the School of Industrial Engineering (ETSII) of the Technical University of Madrid (UPM). The main purpose of this event is to present the ongoing research carried out by professors and researchers of the Institutes, Research Centres, Research Groups and Departments of this School, through funded research projects in close collaboration with public and private institutions and companies, some of them from IBEX-35. This book contains the 138 posters presented from different branches of engineering such as: acoustic, aerospace, bioengineering, chemical, electrical, electronics, automation, energy, environmental, management and industrial organization, laser technology and industrial organization, laser technology and applications, materials, mathematics, statistics, mechanics, manufacturing, structures, nuclear technology, seismic, vehicles and railways.