A pressão intracraniana (PIC) é um dos principais parâmetros neurológicos em animais e humanos. A PIC é uma função da relação entre o conteúdo da caixa craniana (parênquima cerebral, líquido cefalorraquiano e sangue) e o volume do crânio. O aumento da PIC (hipertensão intracraniana) pode acarretar graves efeitos fisiológicos ou até mesmo o óbito em pacientes que não receberem rapidamente os devidos cuidados, os quais incluem o monitoramento em tempo real da PIC. Todos os métodos de monitoramento da PIC atualmente utilizados são invasivos, ou seja, é necessário introduzir um sensor de pressão no sistema nervoso central, acarretando aos pacientes riscos de infecções e traumas decorrentes do método. Neste trabalho desenvolvemos um método minimamente invasivo de monitoramento da pressão intracraniana, que consiste na utilização de sensores de deformação do tipo strain gauge fixados sobre a calota craniana. Os sinais oriundos deste sensor foram amplificados, filtrados e enviados para um computador com software apropriado para análise e armazenamento dos dados. O trabalho aqui apresentado objetivou os testes "in vivo" do sistema, onde foi utilizada mais de uma centena de animais em diversos testes, sendo que em todos os casos os resultados foram satisfatórios, apontando a eficácia do método. / The intracranial pressure (ICP) is one of the most important neurological parameter in animals and humans. The ICP is a function of the relation between the contents of the skull (brain parenchyma, cerebrospinal fluid and blood) and the volume of the skull. The increase in ICP (intracranial hypertension) may cause serious physiological effects and death in patients that do not receive appropriate care quickly, which includes real-time monitoring of ICP. All monitoring methods currently used in ICP are invasive, ie requiring invasion of the central nervous system by a pressure sensor, causing infections and traumas risks to patients. In this work we present a new minimally invasive method to monitor the intracranial pressure. This uses strain gauge deformation sensors, externally glued on the skull. The signal from this sensor is amplified, filtered and sent to a computer with appropriate software for analysis and data storage. "In vitro" and "in vivo" experiments let to the following results: (1) Our minimally invasive system is capable of adequately monitoring the ICP. (2) The measurements are in real and online time providing excellent signal and stability. (3) Simultaneous comparison with invasive methods not only validated our results but showed increased performance. The equipment cost effective will allow the use of our system in the Public Health System, with a important social aspect of our contribution.

This research presents a pulse-by-pulse analysis of Oscillometric blood pressure waveform at systolic, diastolic and mean arterial pressure points. Using a mathematical optimization technique, pulses are characterized into component harmonic by minimizing the least square error. The results at the important pressure points are analyzed and compared for different subject using different waveform extraction techniques. Blood pressure is estimated using the harmonic parameters. The approach studies changes in the parameters as oscillometric blood pressure recording is done. 8 harmonic parameters are obtained from the pulse characterization and are used to estimate Systolic arterial Blood Pressure, Mean arterial Blood Pressure, and Diastolic arterial Blood Pressure. The estimates are compared with our reference value to determine which has the best agreement. The proposed method is further compared with Maximum Amplitude Algorithm and Pulse Morphology Algorithm. The effect of oscillometric waveform extraction methods on the proposed method is observed. The experiment established the fact that the extraction technique can alter the shape of oscillometric pulses. The methods were compared and it was observed that the used extraction methods did not make any significant difference on the accuracy, using this technique.

<p>An interest has been established in the identification, documentation and classifi- cation of the environmental assumptions that are missing from the original PACE- MAKER System Specification. This thesis addresses the presented challenge and documents the procedure used to identify, classify, and document these missing en- vironmental assumptions.</p> <p>In summary, this thesis answers the following questions: <ol> <li></p> <p>What can be done in order to improve the original PACEMAKER System</p> <p>Specification with respect to environmental assumptions? </li> <li></p> <p>Why is it beneficial, in terms of enhancing software quality, to include the doc- umentation of environmental assumptions – which sometimes are (wrongfully) perceived as being collateral and optional – as part of the software requirements document? </li> <li></p> <p>How should such environmental assumptions be documented? </li> </ol></p> <p>More specifically, this thesis • Presents an abstract model for the PACEMAKER system. • Identifies system boundaries and interfaces in the PACEMAKER model. • Identifies environmental assumptions for the PACEMAKER system.</p> <p>• Presents a classification system for the environmental assumptions identified for the PACEMAKER system based on the proposed model.</p> <p>• Proposes a process for identifying environmental assumptions.</p> <p>Furthermore, the research findings presented in this thesis are not limited to the PACEMAKER system. The documentation convention proposed in this thesis is meant to be generalized and can be extended to address similar documentation needs posed by all kinds of software systems. Additionally, the process of environmental assumptions elicitation described in this thesis provides a useful reference for con- ducting similar assumption identification projects. Lastly, the classification system presented in this thesis for the environmental assumptions exhibits one facet of a grander conceptual system – one that incorporates multiple ‘views’ of the same set of assumptions, with each view being distinguished by a unique set of classification criteria.</p> / Master of Applied Science (MASc)

Este trabalho descreve os passos envolvidos no desenvolvimento de um protótipo de aberroscópio para uso oftalmológico. Este instrumento faz incidir no fundo do olho humano um feixe luminoso de baixa potência e amostra, por meio do método de Hartmann, as frentes de onda da luz espalhada. A partir dos dados coletados, a forma das frentes de onda são reconstituídas e as aberrações eventualmente existentes no olho são calculadas e representadas por intermédio dos polinômios de Zernike. Aqui são expostos os fundamentos deste método, algumas das suas propriedades e limitações. Também é mostrada a caracterização funcional do protótipo desenvolvido, testando-o com elementos ópticos de propriedades conhecidas / This work describes the steps involved in the aberroscope prototype development for ophthalmological use. This instrument injects inside the human eye a low power light beam and sample, by Hartmann method, the wavefronts produced by ocular fundus light scattering. From collected data, the wavefront shape is reconstructed and the eye aberrations that eventually existent are calculated and adjusted by Zernike polynomials. Are discussed the method foundations, some of properties and limitations. Also the functional characterization of the developed prototype is shown, by testing it with optical elements of known properties

Este trabalho descreve os passos envolvidos no desenvolvimento de um protótipo de aberroscópio para uso oftalmológico. Este instrumento faz incidir no fundo do olho humano um feixe luminoso de baixa potência e amostra, por meio do método de Hartmann, as frentes de onda da luz espalhada. A partir dos dados coletados, a forma das frentes de onda são reconstituídas e as aberrações eventualmente existentes no olho são calculadas e representadas por intermédio dos polinômios de Zernike. Aqui são expostos os fundamentos deste método, algumas das suas propriedades e limitações. Também é mostrada a caracterização funcional do protótipo desenvolvido, testando-o com elementos ópticos de propriedades conhecidas / This work describes the steps involved in the aberroscope prototype development for ophthalmological use. This instrument injects inside the human eye a low power light beam and sample, by Hartmann method, the wavefronts produced by ocular fundus light scattering. From collected data, the wavefront shape is reconstructed and the eye aberrations that eventually existent are calculated and adjusted by Zernike polynomials. Are discussed the method foundations, some of properties and limitations. Also the functional characterization of the developed prototype is shown, by testing it with optical elements of known properties

Stable and computationally efficient reconstruction methodologies are developed to solve two important medical imaging problems which use near-infrared (NIR) light as the source of interrogation, namely, diffuse optical tomography (DOT) and one of its variations, ultrasound-modulated optical tomography (UMOT). Since in both these imaging modalities the system matrices are ill-conditioned owing to insufficient and noisy data, the emphasis in this work is to develop robust stochastic filtering algorithms which can handle measurement noise and also account for inaccuracies in forward models through an appropriate assignment of a process noise. However, we start with demonstration of speeding of a Gauss-Newton (GN) algorithm for DOT so that a video-rate reconstruction from data recorded on a CCD camera is rendered feasible. Towards this, a computationally efficient linear iterative scheme is proposed to invert the normal equation of a Gauss-Newton scheme in the context of recovery of absorption coefficient distribution from DOT data, which involved the singular value decomposition (SVD) of the Jacobian matrix appearing in the update equation. This has sufficiently speeded up the inversion that a video rate recovery of time evolving absorption coefficient distribution is demonstrated from experimental data. The SVD-based algorithm has made the number of operations in image reconstruction to be rather than. 2()ONN3()ONN The rest of the algorithms are based on different forms of stochastic filtering wherein we arrive at a mean-square estimate of the parameters through computing their joint probability distributions conditioned on the measurement up to the current instant. Under this, the first algorithm developed uses a Bootstrap particle filter which also uses a quasi-Newton direction within. Since keeping track of the Newton direction necessitates repetitive computation of the Jacobian, for all particle locations and for all time steps, to make the recovery computationally feasible, we devised a faster update of the Jacobian. It is demonstrated, through analytical reasoning and numerical simulations, that the proposed scheme, not only accelerates convergence but also yields substantially reduced sample variance in the estimates vis-à-vis the conventional BS filter. Both accelerated convergence and reduced sample variance in the estimates are demonstrated in DOT optical parameter recovery using simulated and experimental data. In the next demonstration a derivative free variant of the pseudo-dynamic ensemble Kalman filter (PD-EnKF) is developed for DOT wherein the size of the unknown parameter is reduced by representing of the inhomogeneities through simple geometrical shapes. Also the optical parameter fields within the inhomogeneities are approximated via an expansion based on the circular harmonics (CH) (Fourier basis functions). The EnKF is then used to recover the coefficients in the expansion with both simulated and experimentally obtained photon fluence data on phantoms with inhomogeneous inclusions. The process and measurement equations in the Pseudo-Dynamic EnKF (PD-EnKF) presently yield a parsimonious representation of the filter variables, which consist of only the Fourier coefficients and the constant scalar parameter value within the inclusion. Using fictitious, low-intensity Wiener noise processes in suitably constructed ‘measurement’ equations, the filter variables are treated as pseudo-stochastic processes so that their recovery within a stochastic filtering framework is made possible. In our numerical simulations we have considered both elliptical inclusions (two inhomogeneities) and those with more complex shapes ( such as an annular ring and a dumbbell) in 2-D objects which are cross-sections of a cylinder with background absorption and (reduced) scattering coefficient chosen as = 0.01 mm-1 and = 1.0 mm-1respectively. We also assume=0.02 mm-1 within the inhomogeneity (for the single inhomogeneity case) and=0.02 and 0.03 mm-1 (for the two inhomogeneities case). The reconstruction results by the PD-EnKF are shown to be consistently superior to those through a deterministic and explicitly regularized Gauss-Newton algorithm. We have also estimated the unknown from experimentally gathered fluence data and verified the reconstruction by matching the experimental data with the computed one. The superiority of a modified version of the PD-EnKF, which uses an ensemble square root filter, is also demonstrated in the context of UMOT by recovering the distribution of mean-squared amplitude of vibration, related to the Young’s modulus, in the ultrasound focal volume. Since the ability of a coherent light probe to pick-up the overall optical path-length change is limited to modulo an optical wavelength, the individual displacements suffered owing to the US forcing should be very small, say within a few angstroms. The sensitivity of modulation depth to changes in these small displacements could be very small, especially when the ROI is far removed from the source and detector. The contrast recovery of the unknown distribution in such cases could be seriously impaired whilst using a quasi-Newton scheme (e.g. the GN scheme) which crucially makes use of the derivative information. The derivative-free gain-based Monte Carlo filter not only remedies this deficiency, but also provides a regularization insensitive and computationally competitive alternative to the GN scheme. The inherent ability of a stochastic filter in accommodating the model error owing to a diffusion approximation of the correlation transport may be cited as an added advantage in the context of the UMOT inverse problem. Finally to speed up forward solve of the partial differential equation (PDE) modeling photon transport in the context of UMOT for which the PDE has time as a parameter, a spectral decomposition of the PDE operator is demonstrated. This allows the computation of the time dependent forward solution in terms of the eigen functions of the PDE operator which has speeded up the forward solution, which in turn has rendered the UMOT parameter recovery computationally efficient.

Ce travail porte sur le développement d’une nouvelle technique de diagnostic associant la résonance magnétique à haute résolution spatiale à la spectroscopie optique d’autofluorescence et de réflectance. La mise au point d’une telle sonde endoluminale bimodale s’inscrit dans les recherches de méthodes complémentaires ou alternatives à l’endoscopie conventionnelle pour le diagnostic précoce des pathologies du tube digestif. En effet le cancer colorectal représente aujourd’hui un enjeu majeur de santé publique avec plus de 1,2 millions de cas diagnostiqués dans le monde sachant que le taux de survie à 5 ans d’un patient est actuellement de 94% dans le cas de lésions détectées à un stade précoce (stade I) et seulement de 8% à un stade tardif (stade IV). Dans la première partie du manuscrit, nous abordons les différentes modalités d’imagerie et d’analyse spectrale en cours de développement ou d’évaluation, en mettant l’accent sur les principes physiques utilisés en RMN et spectroscopie optique. Dans une deuxième partie, nous détaillons la conception et la réalisation de prototypes de sondes endoluminales ainsi que les bancs optiques associés. Nous traitons également de la mise en oeuvre de dispositifs d’acquisition ainsi que des méthodes d’analyse de données au moyen de programmes informatiques dédiés. Dans une dernière partie, le système bimodal est caractérisé et validé lors d’études sur fantômes et une étude in vivo sur lapin. Les images obtenues par RM, fournissant l’information morphologique des échantillons ou du tissu, et les spectres optiques liés à leur composition sont corrélés / The main aim of this work is the development of a new diagnostic technique combining high spatial resolution MRI to autofluorescence and reflectance spectroscopy through the conception of a bimodal endoluminal probe. Such a technique falls within the framework of alternative innovative techniques to conventional colonoscopy that would allow better sensitivity to early stage digestive pathologies. Colorectal cancer is today a major health issue worldwide with more than 1.2 million cases diagnosed each year bearing the fact that the 5 year survival rate is 94% when precancerous lesions are diagnosed at an early stage (stage I) and only 8% when diagnosed at an advanced stage (stage IV). The promising imaging and spectral analysis techniques under investigation or undergoing clinical evaluation in different parts of the world are presented in the first chapter of this manuscript along with the basic physics involved in magnetic resonance imaging and optical spectroscopy. Chapter 2 gives a detailed description of the work carried out in devising and conceiving different endoluminal bimodal probe prototypes along with the dedicated optical test benches. Dedicated data processing and visualisation programmes developed are also presented within this chapter. The final chapter of this work deals with the different studies carried out in-vitro on different phantoms and in-vivo on a rabbit. Morphological information obtained through the MR images are also correlated to the biochemical information through the autofluorescence and reflectance spectra

O procedimento cirúrgico para implantes mamários inclui os chamados medidores, utilizados para a mensuração de volume e geometria antes colocação do implante definitivo na paciente. Esses dispositivos são constituídos por um invólucro de elastômero de silicone grau médico da classe siloxano ou poliuretano e cheios com volumes pré-estabelecidos de gel ou elastômero de silicone, grau médico, sendo apresentados em diversos volumes e formas equivalentes ao volume e forma do implante correspondente. Este trabalho avaliou o processo de limpeza manual dos medidores para implantes, sob o ponto de vista da redução da carga microbiana, propiciando a eficácia do processo de esterilização, nas condições encontradas nos Centros Cirúrgicos Hospitalares e utilizando seus equipamentos usuais. Foram realizados testes de desafio microbiológico em amostras de medidores com superfície texturizada e superfície revestida com poliuretano, utilizando cinco microrganismos (Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Candida albicans e Aspergillus niger) e dois tipos de detergente para comparação: não enzimático e enzimático. Determinou-se a biocarga antes e após a limpeza, e em seguida realizou-se a esterilização a 126°C por 30 minutos (1,4 kgf/cm2) das amostras, que foi avaliada por teste de esterilidade. Os resultados mostraram que a etapa de lavagem contribuiu para a redução de 4 ciclos logarítmicos da população inicialmente considerada e não houve diferença entre os resultados de biocarga dos medidores com superfície texturizada e superfície revestida com poliuretano. O processo de limpeza dos medidores com detergente não enzimático ou enzimático seguido de esterilização apresenta eficiência suficiente para garantir a esterilidade requerida para a utilização dos medidores. / The surgical procedure for mammary implants include the so called sizers, used to measure both volume and geometry prior to the definitive placement in the womans breast. These devices present a silicon elastomer or polyurethane external capsule, medical grade, siloxan class filled with predetermined gel or silicon elastomer volumes, also medical grade and are presented in several shapes and volumes equivalent to the shapes and volumes of the corresponding final implant. This study evaluated the manual cleaning process of the sizers focusing in the bioburden thus rendering an effective sterilization process, under the usual equipment and conditions found in the hospital surgery centers. Microbial challenge tests were performed using 5 microorganisms (Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Candida albicans and Aspergillus niger) and two types of detergent , non enzymatic and enzymatic for comparison. Bioburden was determined before and after the cleaning procedure and after that samples were sterilized at 126°C (1,4 kgf/cm2) for 30 minutes, which was evaluated through sterility testing. Results shown that the cleaning step contributed to a 4 log cycle reduction in the samples initial bioburden and that there was no difference between bioburden results in both types of sizers (textured or polyurethane capsule). The cleaning process using non enzymatic or enzymatic detergents followed by sterilization shows enough effectiveness to ensure the required sterility for using the sizers.

O procedimento cirúrgico para implantes mamários inclui os chamados medidores, utilizados para a mensuração de volume e geometria antes colocação do implante definitivo na paciente. Esses dispositivos são constituídos por um invólucro de elastômero de silicone grau médico da classe siloxano ou poliuretano e cheios com volumes pré-estabelecidos de gel ou elastômero de silicone, grau médico, sendo apresentados em diversos volumes e formas equivalentes ao volume e forma do implante correspondente. Este trabalho avaliou o processo de limpeza manual dos medidores para implantes, sob o ponto de vista da redução da carga microbiana, propiciando a eficácia do processo de esterilização, nas condições encontradas nos Centros Cirúrgicos Hospitalares e utilizando seus equipamentos usuais. Foram realizados testes de desafio microbiológico em amostras de medidores com superfície texturizada e superfície revestida com poliuretano, utilizando cinco microrganismos (Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Candida albicans e Aspergillus niger) e dois tipos de detergente para comparação: não enzimático e enzimático. Determinou-se a biocarga antes e após a limpeza, e em seguida realizou-se a esterilização a 126°C por 30 minutos (1,4 kgf/cm2) das amostras, que foi avaliada por teste de esterilidade. Os resultados mostraram que a etapa de lavagem contribuiu para a redução de 4 ciclos logarítmicos da população inicialmente considerada e não houve diferença entre os resultados de biocarga dos medidores com superfície texturizada e superfície revestida com poliuretano. O processo de limpeza dos medidores com detergente não enzimático ou enzimático seguido de esterilização apresenta eficiência suficiente para garantir a esterilidade requerida para a utilização dos medidores. / The surgical procedure for mammary implants include the so called sizers, used to measure both volume and geometry prior to the definitive placement in the womans breast. These devices present a silicon elastomer or polyurethane external capsule, medical grade, siloxan class filled with predetermined gel or silicon elastomer volumes, also medical grade and are presented in several shapes and volumes equivalent to the shapes and volumes of the corresponding final implant. This study evaluated the manual cleaning process of the sizers focusing in the bioburden thus rendering an effective sterilization process, under the usual equipment and conditions found in the hospital surgery centers. Microbial challenge tests were performed using 5 microorganisms (Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Candida albicans and Aspergillus niger) and two types of detergent , non enzymatic and enzymatic for comparison. Bioburden was determined before and after the cleaning procedure and after that samples were sterilized at 126°C (1,4 kgf/cm2) for 30 minutes, which was evaluated through sterility testing. Results shown that the cleaning step contributed to a 4 log cycle reduction in the samples initial bioburden and that there was no difference between bioburden results in both types of sizers (textured or polyurethane capsule). The cleaning process using non enzymatic or enzymatic detergents followed by sterilization shows enough effectiveness to ensure the required sterility for using the sizers.

The growth of sensors and sensing technologies have made significant impact in our day-to-day life. The five principle sensory organs of our body should perform effectively, so that we can lead a good healthy life. Apart from these natural sensors, there are man-made sensors that helps us to cope with diseases, organ failure etc. and enable us to lead a normal life. In recent years, with the prevalence of new kind of diseases, the need for new type of biomedical sensors is becoming very important. As a result, sensors used for biomedical applications have become an emerging technology and rapidly growing field of research. The aim of the present thesis work is to use the piezoelectric property of Polyvinylidene Fluoride (PVDF) film for the development of biomedical sensor and studying its application for human respiration/breathing related abnormalities. PVDF nasal sensor was designed in cantilever configuration and detailed theoretical analysis of the same was performed. Based on theoretical and experimental results, the PVDF nasal sensor dimensions were optimized. Suitable signal conditioning circuitry was designed and a measurement system for biomedical application was developed. The developed PVDF nasal sensor was calibrated using MEMS low-pressure sensor. The PVDF nasal sensor system has been applied in different biomedical applications namely, (i) to monitor human respiration pattern, (ii) to identify different Respiration Rates (RR), (iii) to evaluate Deviated Nasal Septum (DNS) in comparison with other objective method and, (vi) to clinically investigate nasal obstruction in comparison with subjective method. The thesis is divided into seven chapters. Chapter 1 This chapter gives a general introduction about biomedical sensors, piezoelectric sensing principle and PVDF polymer films along with the relevant literature survey. The brief introduction as well as literature survey of techniques used to monitor human respiration and to measure nasal obstruction is also included in this chapter. Chapter 2 This chapter gives details about the design of the PVDF nasal sensor in the cantilever configuration for sensing nasal airflow along with the relevant theoretical equations. Also, the details on the optimization of the PVDF nasal sensor dimensions based on the theoretical and experimental analysis are presented. Chapter 3 This chapter reports the designing of the necessary signal conditioning hardware along with the data acquisition unit for the PVDF nasal sensor. The signal conditioning hardware unit made consists of charge amplifier, low-pass filter and an amplifier. Besides, a complete measurement system for biomedical application was developed using PVDF nasal sensor and its merits and demerits were discussed. Chapter 4 In this chapter, an experimental set-up for measuring human respiration/breathing pressure using water U-tube manometer has been described. Also, the calibration procedure followed for the developed PVDF nasal sensor using a Micro Electro Mechanical Systems(MEMS) low pressure sensor is reported. Apart from these, the details on the measurement of deflection of the PVDF cantilever sensing element using laser displacement setup are provided. In addition, the PVDF nasal sensor was also calibrated for various air flow rates. At the end, a study has been reported on optimizing the position the PVDF nasal sensor with respect to human nose. Chapter 5 This chapter is divided into two sections, Section 5.1: This section describes the applicability of the PVDF nasal sensor using its piezoelectric property to monitor the human respiration pattern of each nostril simultaneously. The results of the PVDF nasal sensor have also been evaluated by comparing with Respiratory Inductive Plethysmograph(RIP) technique in normal subjects. Section 5.2: In this section, PVDF nasal sensor, RIP and Nasal Prongs (NP) techniques were used to measure the RR of healthy adults. The aim here was to evaluate the presently developed PVDF nasal sensor for identifying different RR compared to „Gold standard‟ RIP and NP methods. Chapter 6 This chapter is divided into two sections. Section 6.1: This section reports about the utilization of the developed PVDF nasal sensor for clinical application on the patient population. For this purpose, the performance of the PVDF nasal sensor measurements has been compared with the Peak Nasal Inspiratory Flow(PNIF) objective technique and visual analog scale (VAS). Section 6.2: This section describes about the use of PVDF nasal sensor system to measure nasal obstruction caused due to DNS objectively. Further, the results of the PVDF nasal sensor were compared with subjective techniques namely, VAS and clinician scale in patients and control group. Chapter 7 This chapter is composed of two sections. Section 7.1: This section summarizes the salient features of the work presented in this thesis. Section 7.2: This section reports a scope for carrying out further work.