The pH of tumors and surrounding tissues is a key biophysical property of the tumor microenvironment that affects how a tumor survives and how it invades the surrounding space of normal tissue. Research into tumorigenesis and tumor treatment is greatly dependent on accurate, precise, and reproducible measurements. Optical imaging is generally regarded as the best choice for non-invasive and high spatial resolution measurements. Ratiometric fluorescence imaging and fluorescence lifetime imaging microscopy (FLIM) are two primary ways for measuring tumor pH.pH measurements in a window chamber animal model using a ratiometric fluorescence imaging technique is demonstrated in this dissertation. The experimental setup, imaging protocols, and results are presented. A significantly varying bias was consistently observed in the measured pH. A comprehensive analysis on the possible error sources accounting for this bias is carried out. The result of analysis reveals that accuracy of ratiometric method is most likely limited by biological and physiological factors.FLIM is a promising alternative because the fluorescence lifetime is insensitive to the biological and physiological factors. Photon noise is the predominant error source of FLIM. The Fisher information matrix and the Cramér-Rao lower bound are used to calculate the lowest possible variance of estimated lifetime for time-domain (TD) FLIM. A statistical analysis of frequency-domain (FD) FLIM using homodyne lock-in detection is also performed and the probability density function of the estimated lifetime is derived. The results allow the derivation of the optimum experimental parameters, which yields the lowest variance of the estimated lifetime in a given period of imaging time. The analyses of both TD and FD-FLIM agree with results of corresponding Monte Carlo simulations.

Orientador: Zacarias Xavier de Barros / Banca: José Milton Arana / Banca: Osmar Delmanto Junior / Banca: Lincoln Gering Cardoso / Banca: Vilmar Antonio Rodrigues / Resumo: Neste trabalho, foram realizados levantamentos topográficos para a avaliação do efeito da cobertura vegetal, na recepção de sinais GPS, para obtenção de posicionamento tri-dimensional, considerando os estudos realizados em diferentes tipos de uso do solo. Vértices foram implantados em diferentes tipos de uso do solo; em área com pastagem, com plantação de seringueiras e com eucaliptos, e as suas posições determinadas com estação total, nivelamento geométrico e com receptores GPS. Na avaliação do posicionamento altimétrico adotou-se como valores de referência os desníveis determinados com o nivelamento geométrico para avaliação dos dados obtidos com receptores GPS. As coordenadas planimétricas obtidas com receptores GPS foram analisadas utilizando-se com valores de referência os dados obtidos com a estação total. No levantamento topográfico com estação total foram adotadas as prescrições estabelecidas nas Normas da Associação Brasileira de Normas Técnicas (ABNT) NBR 13.133, Execução de Levantamentos Topográficos, para poligonais do tipo IVP. Foi realizada a análise de exatidão e de precisão do posicionamento tridimensional, adotando como padrão a NBR 13133 da ABNT para a classe do levantamento executado. Para aplicações do GPS na altimetria há necessidade do conhecimento da ondulação geoidal (N), que neste trabalho, para a sua determinação foram coletados dados com receptor na referência de nível (RN). Os resultados obtidos indicam que cuidados especiais devem ser tomados nos levantamentos com receptores GPS em áreas com cobetura vegetal, pois estas interferem na propagação das ondas eletromagnéticas provenientes dos satélites podendo inviabilizar o posicionamento. / In this work, topographic surveys were carried out in order to evaluate the effect of vegetal cover, on the reception of GPS signals, for 3D positioning, considering studies to be made in different types of land use. Points were set up on different types of land use, in areas containing grass, rubber trees and eucalyptus, which had their positions defined using a total station, geometric leveling and GPS receivers In the evaluation of height positioning it was adopted as reference values the height differences determined by geometric levelling in order to evaluate data obtained through GPS receivers. Planimetric coordinates obtained by using GPS receivers were analysed using as reference values the data obtained using a total station. During the topographic survey using a total station the recommendations set up by the Brazilian Association for Technical Rules (ABNT) NBR 13.133, regarding the execution of topographic surveys, for transverses of type IVP. Accuracy and precision analysis was made on the 3D positioning, also considering ABNT NBR 13.133, for the class of topographic survey which was carried out. In order to apply GPS on height positiong it is necessary to know the geoidal ondulation (N) and, in this work, N was computed based upon data acquired employing receivers at the level reference (RN). The results obtained indicate that special care must be taken during the surveys carried out with the use of GPS receivers on areas with vegetal cover, because it causes interference in the propagation of electromagnetic waves from the satellite which can even make the positioning become unviable. / Doutor

International Telemetering Conference Proceedings / October 23-26, 2000 / Town & Country Hotel and Conference Center, San Diego, California / Range to an orbiting satellite from a ground reference point (ground station) can be determined by measuring the round trip time for a waveform transmitted to the satellite and returned to the ground station (Turnaround Ranging) and more recently by using the Global Positioning System (GPS). This paper first summarizes and compares the two approaches. The paper then describes and analyzes a new turn-around ranging system which uses a flexible ranging waveform that provides spectral compatibility with existing Military, NASA, and Commercial satellite uplink/downlink signals.

Made available in DSpace on 2014-06-11T19:31:38Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-10-01Bitstream added on 2014-06-13T19:42:00Z : No. of bitstreams: 1 itame_oy_dr_botfca.pdf: 795304 bytes, checksum: f5cd4e866ab892ec4c244173b15a3d6e (MD5) / Neste trabalho, foram realizados levantamentos topográficos para a avaliação do efeito da cobertura vegetal, na recepção de sinais GPS, para obtenção de posicionamento tri-dimensional, considerando os estudos realizados em diferentes tipos de uso do solo. Vértices foram implantados em diferentes tipos de uso do solo; em área com pastagem, com plantação de seringueiras e com eucaliptos, e as suas posições determinadas com estação total, nivelamento geométrico e com receptores GPS. Na avaliação do posicionamento altimétrico adotou-se como valores de referência os desníveis determinados com o nivelamento geométrico para avaliação dos dados obtidos com receptores GPS. As coordenadas planimétricas obtidas com receptores GPS foram analisadas utilizando-se com valores de referência os dados obtidos com a estação total. No levantamento topográfico com estação total foram adotadas as prescrições estabelecidas nas Normas da Associação Brasileira de Normas Técnicas (ABNT) NBR 13.133, Execução de Levantamentos Topográficos, para poligonais do tipo IVP. Foi realizada a análise de exatidão e de precisão do posicionamento tridimensional, adotando como padrão a NBR 13133 da ABNT para a classe do levantamento executado. Para aplicações do GPS na altimetria há necessidade do conhecimento da ondulação geoidal (N), que neste trabalho, para a sua determinação foram coletados dados com receptor na referência de nível (RN). Os resultados obtidos indicam que cuidados especiais devem ser tomados nos levantamentos com receptores GPS em áreas com cobetura vegetal, pois estas interferem na propagação das ondas eletromagnéticas provenientes dos satélites podendo inviabilizar o posicionamento. / In this work, topographic surveys were carried out in order to evaluate the effect of vegetal cover, on the reception of GPS signals, for 3D positioning, considering studies to be made in different types of land use. Points were set up on different types of land use, in areas containing grass, rubber trees and eucalyptus, which had their positions defined using a total station, geometric leveling and GPS receivers In the evaluation of height positioning it was adopted as reference values the height differences determined by geometric levelling in order to evaluate data obtained through GPS receivers. Planimetric coordinates obtained by using GPS receivers were analysed using as reference values the data obtained using a total station. During the topographic survey using a total station the recommendations set up by the Brazilian Association for Technical Rules (ABNT) NBR 13.133, regarding the execution of topographic surveys, for transverses of type IVP. Accuracy and precision analysis was made on the 3D positioning, also considering ABNT NBR 13.133, for the class of topographic survey which was carried out. In order to apply GPS on height positiong it is necessary to know the geoidal ondulation (N) and, in this work, N was computed based upon data acquired employing receivers at the level reference (RN). The results obtained indicate that special care must be taken during the surveys carried out with the use of GPS receivers on areas with vegetal cover, because it causes interference in the propagation of electromagnetic waves from the satellite which can even make the positioning become unviable.

This thesis is titled "A Framework for Enhancing the Accuracy of Ultra Precision Machining." In this thesis unwanted relative tool / workpiece vibration is identified as a major contributor to workpiece inaccuracy. The phenomenon is studied via in situ vibrational measurements during cutting and also by the analysis of the workpiece surface metrology of ultra precision diamond face turned aluminum 6061-T6. The manifestation of vibrations in the feed and in-feed directions of the workpiece was studied over a broadband of disturbance frequencies. It is found that the waviness error measured on the cut workpiece surface was significantly larger than that caused by the feed marks during cutting. Thus it was established that unwanted relative tool / workpiece vibrations are the dominant source of surface finish error in ultra precision machining. By deriving representative equations in the polar coordinate system, it was found that the vibrational pattern repeats itself, leading to what are referred to in this thesis as surface finish lobes. The surface finish lobes describe the waviness or form error associated with a particular frequency of unwanted relative tool / workpiece vibration, given a particular feed rate and spindle speed. With the surface finish lobes, the study of vibrations is both simplified and made more systematic. Knowing a priori the wavelength range caused by relative tool / workpiece vibration also allows one to extract considerable vibration content information from a small white light interferometry field of view. It was demonstrated analytically that the error caused by relative tool / workpiece vibration is always distinct from the surface roughness caused by the feed rate. It was also shown that the relative tool / workpiece vibration-induced wavelength in the feed direction has a limited and repeating range. Additionally, multiple disturbance frequencies can produce the same error wavelength on the workpiece surface. Since the meaningful error wavelength range is finite given the size of the part and repeating, study then focussed on this small and manageable range of wavelengths. This range of wavelengths in turn encompasses a broadband range of possible disturbance frequencies, due to the repetition described by the surface finish lobes. Over this finite range of wavelengths, for different machining conditions, the magnitude of the waviness error resulting on the cut workpiece surface was compared with the actual relative tool / workpiece vibrational magnitude itself. It was found that several opportunities occur in ultra precision machining to mitigate the vibrational effect on the workpiece surface. The first opportunity depends only on the feed rate and spindle speed. Essentially, it is possible to force the wavelength resulting from an unwanted relative tool / workpiece vibration to a near infinite length, thus eliminating its effect in the workpiece feed direction. Further, for a given disturbance frequency, various speed and feed rate combinations are capable of producing this effect. However, this possibility exists only when a single, dominant and fixed disturbance frequency is present in the process. By considering the tool nose geometry, depth of cut, and vibrational amplitude over the surface finish lobe finite range, it was found that the cutting parameters exhibit an attenuating or filtering effect on vibrations. Thus, cutting parameters serve to mitigate the vibrational effect on the finished workpiece over certain wavelengths. The filter curves associated with various feed rates were compared. These filter curves describe the magnitude of error on the ultra precision face turned workpiece surface compared with the original unwanted tool / workpiece vibrational magnitude. It was demonstrated with experimental data that these filter curves are physically evident on the ultra precision diamond face turned workpiece surface. It was further shown that the surface roughness on the workpiece surface caused by the feed rate was reduced with relative tool / workpiece vibrations, and in some cases the feed mark wavelength was changed altogether. Mean arithmetic surface roughness curves were also constructed, and the filtering phenomenon was demonstrated over a broadband of disturbance frequencies. It is well established that a decrease in the feed rate reduces the surface roughness in machining. However, it was demonstrated that the improved surface finish observed with a slower feed rate in ultra precision diamond face turning was actually because it more effectively mitigated the vibrational effect on the workpiece surface over a broadband of disturbance frequencies. Experimental findings validated this observation. By only considering the effect of vibrations on the surface finish waviness error, it was shown that the workpiece diamond face turned with a feed rate of 2 {tm / rev has a mean arithmetic surface roughness, Ra , that was 43 per cent smaller than when a feed rate of 10 μm / rev was used. / Thesis / Doctor of Philosophy (PhD)

Autosomal dominant polycystic disease (ADPKD) is the most common hereditary renal disease and is characterized by renal cyst growth and enlargement. Hypertension occurs early when renal function is normal and is characterized by decreased renal blood flow. Accordingly, the measurement of blood flow in the renal arteries can be a valuable tool in evaluating disease progression. In studies performed in conjunction with this work, blood flow was measured through the renal arteries using magnetic resonance imaging (MRI). In order to validate these in vivo measurements, a vascular phantom was created using polyvinyl alcohol (PVA) and also scanned using MRI under controlled steady flow conditions. Ranges of vessel diameters and flow velocities were used to simulate actual flow in a normal and diseased population of adults and children. With the vessel diameters studied in this experiment, minimization of field of view and an increase in spatial resolution is important in obtaining accurate data. However, a significant difference does not exist between the results when using the 160 or 200 mm FOV. An increase in the number of phase encodings provides improved results, although an increase in image acquisition time is observed. Velocity-encoding in all three orthogonal directions does not improve image data. This method of using MRI to measure flow through a vessel is shown to be both accurate and reproducible, and the protocol providing the most correct results is prescribed. Breath-hold phase-velocity encoded MRI proves to be an accurate and reproducible technique in capturing flow and has the potential to be used for the purpose of observing hemodynamic changes in the renal arteries with the progression of ADPKD.

The BOLD contrast employed in functional MRI studies is an ambiguous signal composed of changes in blood flow, blood volume and oxidative metabolism. In situations where the vasculature and metabolism may have been affected, such as in aging and in certain diseases, the dissociation of the more physiologically-specific components from the BOLD signal becomes crucial. The latest generation of calibrated functional MRI methods allows the estimation of both resting blood flow and absolute oxygen metabolism. The work presented here is based on one such proof-of-concept approach, dubbed QUO2, whereby taking into account, within a generalized model, both arbitrary changes in blood flow and blood O2 content during a combination of hypercapnia and hyperoxia breathing manipulations, yields voxel-wise estimates of resting oxygen extraction fraction and oxidative metabolism. In the first part of this thesis, the QUO2 acquisition protocol and data analysis were revisited in order to enhance the temporal stability of individual blood flow and BOLD responses, consequently improving reliability of the model-derived estimates. Thereafter, an assessment of the within and between-subject variability of the optimized QUO2 measurements was performed on a group of healthy volunteers. In parallel, an analysis was performed of the sensitivity of the model to different sources of random and systematic errors, respectively due to errors in measurements and choice of assumed parameters values. Moreover, the various impacts of the oxygen concentration administered during the hyperoxia manipulation were evaluated through a simulation and experimentally, indicating that a mild hyperoxia was beneficial. Finally, the influence of Alzheimer’s disease in vascular and metabolic changes was explored for the first time by applying the QUO2 approach in a cohort of probable Alzheimer’s disease patients and age-matched control group. Voxel-wise and region-wise differences in resting blood flow, oxygen extraction fraction, oxidative metabolism, transverse relaxation rate constant R2* and R2* changes during hypercapnia were identified. A series of limitations along with recommended solutions was given with regards to the delayed transit time, the susceptibility artifacts and the challenge of performing a hypercapnia manipulation in cohorts of elderly and Alzheimer’s patients. / Le contraste BOLD employé dans les études d’imagerie par résonance magnétique fonctionnelle (IRMf) provient d’une combinaison ambigüe de changements du flux sanguin cérébral, du volume sanguin ainsi que du métabolisme oxydatif. Dans un contexte où les fonctions vasculaires ou métaboliques du cerveau ont pu être affectées, tel qu’avec l’âge ou certaines maladies, il est crucial d’effectuer une décomposition du signal BOLD en composantes physiologiquement plus spécifiques. La dernière génération de méthodes d’IRMf calibrée permet d’estimer à la fois le flux sanguin cérébral et le métabolisme oxydatif au repos. Le présent travail est basé sur une telle technique, appelée QUantitative O2 (QUO2), qui, via un model généralisé, prend en considération les changements du flux sanguin ainsi que ceux en concentrations sanguine d’O2 durant des périodes d’hypercapnie et d’hyperoxie, afin d’estimer, à chaque voxel, la fraction d’extraction d’oxygène et le métabolisme oxydatif au repos. Dans la première partie de cette thèse, le protocole d’acquisition ainsi que la stratégie d’analyse de l’approche QUO2 ont été revus afin d’améliorer la stabilité temporelle des réponses BOLD et du flux sanguin, conséquemment, afin d’accroître la fiabilité des paramètres estimés. Par la suite, une évaluation de la variabilité intra- et inter-sujet des différentes mesures QUO2 a été effectuée auprès d’un groupe de participants sains. En parallèle, une analyse de la sensibilité du model à différentes sources d’erreurs aléatoires (issues des mesures acquises) et systématiques (dues aux assomptions du model) a été réalisée. De plus, les impacts du niveau d’oxygène administré durant les périodes d’hyperoxie ont été évalués via une simulation puis expérimentalement, indiquant qu’une hyperoxie moyenne était bénéfique. Finalement, l’influence de la maladie d’Alzheimer sur les changements vasculaires et métaboliques a été explorée pour la première fois en appliquant le protocole QUO2 à une cohorte de patients Alzheimer et à un groupe témoin du même âge. Des différences en terme de flux sanguin, fraction d’oxygène extraite, métabolisme oxydatif, et taux de relaxation transverse R2* au repos comme en réponse à l’hypercapnie, ont été identifiées au niveau du voxel, ainsi qu’au niveau de régions cérébrales vulnérables à la maladie d’Alzheimer. Une liste de limitations accompagnées de recommandations a été dressée en ce qui a trait au temps de transit différé, aux artéfacts de susceptibilité magnétique, de même qu’au défi que représente l’hypercapnie chez les personnes âgées ou atteintes de la maladie d’Alzheimer.