Research lines in Hyperthermia at the Bioinstrumentation Laboratory of the Centre for Biomedical Technology

The Bioinstrumentation Laboratory belongs to the Centre for Biomedical Technology (CTB) of the Technical University of Madrid and its main objective is to provide the scientific community with devices and techniques for the characterization of micro and nanostructures and consequently finding their best biomedical applications. Hyperthermia (greek word for “overheating”) is defined as the phenomenon that occurs when a body is exposed to an energy generating source that can produce a rise in temperature (42-45ºC) for a given time [1]. Specifically, the aim of the hyperthermia methods used in The Bioinstrumentation Laboratory is the development of thermal therapies, some of these using different kinds of nanoparticles, to kill cancer cells and reduce the damage on healthy tissues. The optical hyperthermia is based on noble metal nanoparticles and laser irradiation. This kind of nanoparticles has an immense potential associated to the development of therapies for cancer on account of their Surface Plasmon Resonance (SPR) enhanced light scattering and absorption. In a short period of time, the absorbed light is converted into localized heat, so we can take advantage of these characteristics to heat up tumor cells in order to obtain the cellular death [2]. In this case, the laboratory has an optical hyperthermia device based on a continuous wave laser used to kill glioblastoma cell lines (1321N1) in the presence of gold nanorods (Figure 1a). The wavelength of the laser light is 808 nm because the penetration of the light in the tissue is deeper in the Near Infrared Region. The first optical hyperthermia results show that the laser irradiation produces cellular death in the experimental samples of glioblastoma cell lines using gold nanorods but is not able to decrease the cellular viability of cancer cells in samples without the suitable nanorods (Figure 1b) [3]. The generation of magnetic hyperthermia is performed through changes of the magnetic induction in magnetic nanoparticles (MNPs) that are embedded in viscous medium. The Figure 2 shows a schematic design of the AC induction hyperthermia device in magnetic fluids. The equipment has been manufactured at The Bioinstrumentation Laboratory. The first block implies two steps: the signal selection with frequency manipulation option from 9 KHz to 2MHz, and a linear output up to 1500W. The second block is where magnetic field is generated ( 5mm, 10 turns). Finally, the third block is a software control where the user can establish initial parameters, and also shows the temperature response of MNPs due to the magnetic field applied [4-8]. The Bioinstrumentation Laboratory in collaboration with the Mexican company MRI-DT have recently implemented a new research line on Nuclear Magnetic Resonance Hyperthermia, which is sustained on the patent US 7,423,429B2 owned by this company. This investigation is based on the use of clinical MRI equipment not only for diagnosis but for therapy [9]. This idea consists of two main facts: Magnetic Resonance Imaging can cause focal heating [10], and the differentiation in resonant frequency between healthy and cancer cells [11]. To produce only heating in cancer cells when the whole body is irradiated, it is necessary to determine the specific resonant frequency of the target, using the information contained in the spectra of the area of interest. Then, special RF pulse sequence is applied to produce fast excitation and relaxation mechanism that generates temperature increase of the tumor, causing cellular death or metabolism malfunction that stops cellular division

Alternative method for the metrological characterization of spur gears in the sub-millimeter range using optical equipment

The aim of this work is to develop a software that allows the inspection of spur gear manufactured in the sub-millimeter range. The measurements are made using a digital optical machine and using an analysis proprietary software implemented in Matlab®, which is able to handle images, captured using the digital optical machine. The software allows to evaluate the profile and pitch deviations as establish in the ISO/TR 10064-1:1992 standard

Towards Openness in Biomedical Informatics

Over the last years, and particularly in the context of the COMBIOMED network, our biomedical informatics (BMI) group at the Universidad Politecnica de Madrid has carried out several approaches to address a fundamental issue: to facilitate open access and retrieval to BMI resources —including software, databases and services. In this regard, we have followed various directions: a) a text mining-based approach to automatically build a “resourceome”, an inventory of open resources, b) methods for heterogeneous database integration —including clinical, -omics and nanoinformatics sources—; c) creating various services to provide access to different resources to African users and professionals, and d) an approach to facilitate access to open resources from research projects

The Learning of the subject Biology in a Master in Biomedical Physics

BIOLOGY is a dynamic and fascinating science. The study of this subject is an amazing trip for all the students that have a first contact with this subject. Here, we present the development of the study and learning experience of this subject belonging to an area of knowledge that is different to the training curriculum of students who have studied Physics during their degree period. We have taken a real example, the “Elements of Biology” subject, which is taught as part of the Official Biomedical Physics Master, at the Physics Faculty, of the Complutense University of Madrid, since the course 2006/07. Its main objective is to give to the student an understanding how the Physics can have numerous applications in the Biomedical Sciences area, giving the basic training to develop a professional, academic or research career. The results obtained when we use new virtual tools combined with the classical learning show that there is a clear increase in the number of persons that take and pass the final exam. On the other hand, this new learning strategy is well received by the students and this is translated to a higher participation and a decrease of the giving the subject up

Signal analysis and feature generation for pattern identification of partial discharges in high-voltage equipment

This paper proposes a method for the identification of different partial discharges (PDs) sources through the analysis of a collection of PD signals acquired with a PD measurement system. This method, robust and sensitive enough to cope with noisy data and external interferences, combines the characterization of each signal from the collection, with a clustering procedure, the CLARA algorithm. Several features are proposed for the characterization of the signals, being the wavelet variances, the frequency estimated with the Prony method, and the energy, the most relevant for the performance of the clustering procedure. The result of the unsupervised classification is a set of clusters each containing those signals which are more similar to each other than to those in other clusters. The analysis of the classification results permits both the identification of different PD sources and the discrimination between original PD signals, reflections, noise and external interferences. The methods and graphical tools detailed in this paper have been coded and published as a contributed package of the R environment under a GNU/GPL license.

3D Wavelet-based Fusion Techniques for Biomedical Imaging

Hoy en día las técnicas de adquisición de imágenes tridimensionales son comunes en diversas áreas, pero cabe destacar la relevancia que han adquirido en el ámbito de la imagen biomédica, dentro del cual encontramos una amplia gama de técnicas como la microscopía confocal, microscopía de dos fotones, microscopía de fluorescencia mediante lámina de luz, resonancia magnética nuclear, tomografía por emisión de positrones, tomografía de coherencia óptica, ecografía 3D y un largo etcétera. Un denominador común de todas esas aplicaciones es la constante necesidad por aumentar la resolución y la calidad de las imágenes adquiridas. En algunas de dichas técnicas de imagen tridimensional se da una interesante situación: aunque que cada volumen adquirido no contiene información suficiente para representar el objeto bajo estudio dentro de los parámetros de calidad requeridos por algunas aplicaciones finales, el esquema de adquisición permite la obtención de varios volúmenes que representan diferentes vistas de dicho objeto, de tal forma que cada una de las vistas proporciona información complementaria acerca del mismo. En este tipo de situación es posible, mediante la combinación de varias de esas vistas, obtener una mejor comprensión del objeto que a partir de cada una de ellas por separado. En el contexto de esta Tesis Doctoral se ha propuesto, desarrollado y validado una nueva metodología de proceso de imágenes basada en la transformada wavelet disc¬reta para la combinación, o fusión, de varias vistas con información complementaria de un mismo objeto. El método de fusión propuesto aprovecha la capacidad de descom¬posición en escalas y orientaciones de la transformada wavelet discreta para integrar en un solo volumen toda la información distribuida entre el conjunto de vistas adquiridas. El trabajo se centra en dos modalidades diferentes de imagen biomédica que per¬miten obtener tales adquisiciones multi-vista. La primera es una variante de la micro¬scopía de fluorescencia, la microscopía de fluorescencia mediante lámina de luz, que se utiliza para el estudio del desarrollo temprano de embriones vivos en diferentes modelos animales, como el pez cebra o el erizo de mar. La segunda modalidad es la resonancia magnética nuclear con realce tardío, que constituye una valiosa herramienta para evaluar la viabilidad del tejido miocárdico en pacientes con diversas miocardiopatías. Como parte de este trabajo, el método propuesto ha sido aplicado y validado en am¬bas modalidades de imagen. En el caso de la aplicación a microscopía de fluorescencia, los resultados de la fusión muestran un mejor contraste y nivel de detalle en comparación con cualquiera de las vistas individuales y el método no requiere de conocimiento previo acerca la función de dispersión puntual del sistema de imagen. Además, los resultados se han comparado con otros métodos existentes. Con respecto a la aplicación a imagen de resonancia magnética con realce tardío, los volúmenes fusionados resultantes pre-sentan una mejora cuantitativa en la nitidez de las estructuras relevantes y permiten una interpretación más sencilla y completa de la compleja estructura tridimensional del tejido miocárdico en pacientes con cardiopatía isquémica. Para ambas aplicaciones los resultados de esta tesis se encuentran actualmente en uso en los centros clínicos y de investigación con los que el autor ha colaborado durante este trabajo. Además se ha puesto a libre disposición de la comunidad científica la implementación del método de fusión propuesto. Por último, se ha tramitado también una solicitud de patente internacional que cubre el método de visualización desarrollado para la aplicación de Resonancia Magnética Nuclear. Abstract Nowadays three dimensional imaging techniques are common in several fields, but es-pecially in biomedical imaging, where we can find a wide range of techniques including: Laser Scanning Confocal Microscopy, Laser Scanning Two Photon Microscopy, Light Sheet Fluorescence Microscopy, Magnetic Resonance Imaging, Positron Emission To-mography, Optical Coherence Tomography, 3D Ultrasound Imaging, etc. A common denominator of all those applications being the constant need for further increasing resolution and quality of the acquired images. Interestingly, in some of the mentioned three-dimensional imaging techniques a remarkable situation arises: while a single volume does not contain enough information to represent the object being imaged within the quality parameters required by the final application, the acquisition scheme allows recording several volumes which represent different views of a given object, with each of the views providing complementary information. In this kind of situation one can get a better understanding of the object by combining several views instead of looking at each of them separately. Within such context, in this PhD Thesis we propose, develop and test new image processing methodologies based on the discrete wavelet transform for the combination, or fusion, of several views containing complementary information of a given object. The proposed fusion method exploits the scale and orientation decomposition capabil¬ities of the discrete wavelet transform to integrate in a single volume all the available information distributed among the set of acquired views. The work focuses in two different biomedical imaging modalities which provide such multi-view datasets. The first one is a particular fluorescence microscopy technique, Light-Sheet Fluorescence Microscopy, used for imaging and gaining understanding of the early development of live embryos from different animal models (like zebrafish or sea urchin). The second is Delayed Enhancement Magnetic Resonance Imaging, which is a valuable tool for assessing the viability of myocardial tissue on patients suffering from different cardiomyopathies. As part of this work, the proposed method was implemented and then validated on both imaging modalities. For the fluorescence microscopy application, the fusion results show improved contrast and detail discrimination when compared to any of the individual views and the method does not rely on prior knowledge of the system’s point spread function (PSF). Moreover, the results have shown improved performance with respect to previous PSF independent methods. With respect to its application to Delayed Enhancement Magnetic Resonance Imaging, the resulting fused volumes show a quantitative sharpness improvement and enable an easier and more complete interpretation of complex three-dimensional scar and heterogeneous tissue information in ischemic cardiomyopathy patients. In both applications, the results of this thesis are currently in use in the clinical and research centers with which the author collaborated during his work. An imple¬mentation of the fusion method has also been made freely available to the scientific community. Finally, an international patent application has been filed covering the visualization method developed for the Magnetic Resonance Imaging application.

Criteria for Positioning Active Multilateration Stations Located Close to Distance Measuring Equipment

The need for the use of another surveillance system when radar cannot be used is the reason for the development of the Multilateration (MLT) Systems. However, there are many systems that operate in the L-Band (960-1215MHz) that could produce interference between systems. At airports, some interference has been detected between transmissions of MLT systems (1030MHz and 1090MHz) and Distance Measuring Equipment (DME) (960-1215MHz).

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.

CDAPubMed: a browser extension to retrieve EHR-based biomedical literature

Over the last few decades, the ever-increasing output of scientific publications has led to new challenges to keep up to date with the literature. In the biomedical area, this growth has introduced new requirements for professionals, e.g., physicians, who have to locate the exact papers that they need for their clinical and research work amongst a huge number of publications. Against this backdrop, novel information retrieval methods are even more necessary. While web search engines are widespread in many areas, facilitating access to all kinds of information, additional tools are required to automatically link information retrieved from these engines to specific biomedical applications. In the case of clinical environments, this also means considering aspects such as patient data security and confidentiality or structured contents, e.g., electronic health records (EHRs). In this scenario, we have developed a new tool to facilitate query building to retrieve scientific literature related to EHRs. Results: We have developed CDAPubMed, an open-source web browser extension to integrate EHR features in biomedical literature retrieval approaches. Clinical users can use CDAPubMed to: (i) load patient clinical documents, i.e., EHRs based on the Health Level 7-Clinical Document Architecture Standard (HL7-CDA), (ii) identify relevant terms for scientific literature search in these documents, i.e., Medical Subject Headings (MeSH), automatically driven by the CDAPubMed configuration, which advanced users can optimize to adapt to each specific situation, and (iii) generate and launch literature search queries to a major search engine, i.e., PubMed, to retrieve citations related to the EHR under examination. Conclusions: CDAPubMed is a platform-independent tool designed to facilitate literature searching using keywords contained in specific EHRs. CDAPubMed is visually integrated, as an extension of a widespread web browser, within the standard PubMed interface. It has been tested on a public dataset of HL7-CDA documents, returning significantly fewer citations since queries are focused on characteristics identified within the EHR. For instance, compared with more than 200,000 citations retrieved by breast neoplasm, fewer than ten citations were retrieved when ten patient features were added using CDAPubMed. This is an open source tool that can be freely used for non-profit purposes and integrated with other existing systems.

On a meaningful integration of web services in data-intensive biomedical environments: The DICODE approach

This paper reports on an innovative approach that aims to reduce information management costs in data-intensive and cognitively-complex biomedical environments. Recognizing the importance of prominent high-performance computing paradigms and large data processing technologies as well as collaboration support systems to remedy data-intensive issues, it adopts a hybrid approach by building on the synergy of these technologies. The proposed approach provides innovative Web-based workbenches that integrate and orchestrate a set of interoperable services that reduce the data-intensiveness and complexity overload at critical decision points to a manageable level, thus permitting stakeholders to be more productive and concentrate on creative activities.

Development of FEM/BEM and SEA models from experimental results for structural elements with attached equipment

This work focuses on the analysis of a structural element of MetOP-A satellite. Given the special interest in the influence of equipment installed on structural elements, the paper studies one of the lateral faces on which the Advanced SCATterometer (ASCAT) is installed. The work is oriented towards the modal characterization of the specimen, describing the experimental set-up and the application of results to the development of a Finite Element Method (FEM) model to study the vibro-acoustic response. For the high frequency range, characterized by a high modal density, a Statistical Energy Analysis (SEA) model is considered, and the FEM model is used when modal density is low. The methodology for developing the SEA model and a compound FEM and Boundary Element Method (BEM) model to provide continuity in the medium frequency range is presented, as well as the necessary updating, characterization and coupling between models required to achieve numerical models that match experimental results.

Testing equipment for the improvement of mechanical devices to minimize damage to fruit in commercial packing lines.

Damages -reduced in fruit packing lines is a major cause of grace reduction and quality loos in fresh marks: fruit. Fruit must be treated gently during in sir handling to improve their qualityin order to get a good price in a competitive market. The correct post-hardvest handling in fruit packing lines is a prerequisite to cut down the heavy post-harvest losses. Fruit packing lines must be evaluated, studying their design, the impacts applied to the fruits, the characteristics of the materials, etc. This study establishes the possibility of carrying out modifications and tests in a packing line during a long period of time. For this purpose, an experimental fruit packing line has been designed and located in the Agricultural Engineering Department of the Polythecnic University of Madrid with the aim of improving mechanical devices and fruit handling conditions to minimize damage to fruit. The experimental line consists of several transporting belts, one rollers transporter, one sizer, one elevator, one singularizer, and three trays to receive the calibrated fruit. The line has a length of 6.15 m and a width cf 1.9 m. Movement of the different components is regulated by electric motors with variable velocity electronically controlled. The height of the transfer points is variable and can be easily modified. The experimental line has been calibrated using two instrumented spheres IS 100 (8.8 cm Ø and6.2cm Ø). Average acceleration values obtained in all the transfers of the experimental line lay under 80 g's, although there is big variation for some of them being some values above 100 g's.

INFOBIOMED: European Network of Excellence on Biomedical Informatics to support individualised healthcare

INFOBIOMED is an European Network of Excellence (NoE) funded by the Information Society Directorate-General of the European Commission (EC). A consortium of European organizations from ten different countries is involved within the network. Four pilots, all related to linking clinical and genomic information, are being carried out. From an informatics perspective, various challenges, related to data integration and mining, are included.

A novel scanning lens instrument for evaluating Fresnel lens performance: equipment development and initial results

A system dedicated to the optical transmittance characterization of Fresnel lenses has been developed at NREL, in collaboration with the UPM. The system quantifies the optical efficiency of the lens by generating a performance map. The shape of the focused spot may also be analyzed to understand change in the lens performance. The primary instrument components (lasers and CCD detector) have been characterized to confirm their capability for performing optical transmittance measurements. Measurements performed on SoG and PMMA lenses subject to a variety of indoor conditions (e.g., UV and damp heat) identified differences in the optical efficiency of the evaluated lenses, demonstrating the ability of the Scanning Lens Instrument (SLI) to distinguish between the aged lenses.

Signal analysis and feature generation for pattern identification of partial discharges in high-voltage equipment

This paper proposes a method for the identification of different partial discharges (PDs) sources through the analysis of a collection of PD signals acquired with a PD measurement system. This method, robust and sensitive enough to cope with noisy data and external interferences, combines the characterization of each signal from the collection, with a clustering procedure, the CLARA algorithm. Several features are proposed for the characterization of the signals, being the wavelet variances, the frequency estimated with the Prony method, and the energy, the most relevant for the performance of the clustering procedure. The result of the unsupervised classification is a set of clusters each containing those signals which are more similar to each other than to those in other clusters. The analysis of the classification results permits both the identification of different PD sources and the discrimination between original PD signals, reflections, noise and external interferences. The methods and graphical tools detailed in this paper have been coded and published as a contributed package of the R environment under a GNU/GPL license.