Este trabalho apresenta o estudo de propriedades espectroscópicas de Vidros Oxifluoroboratos de Chumbo, 40PbO-10PbF2-50B2O3 dopados com diferentes concentrações de Dy3+: 1, 3, 5 e 7 mol%. Para tanto foram empregadas as técnicas de Difração de Raios-X, Espalhamento Raman, Absorção Óptica e Fotoluminescência. Parâmetros como temperatura de transição vítrea, índice de refração e densidade também foram determinados. O comportamento do índice de refração, da densidade, e da temperatura de transição vítrea, Tg, indicaram uma possível mudança estrutural provocada pela adição de dopante, o que foi confirmado pela Espectroscopia Raman. Com as medidas de absorção óptica foram calculados os parâmetros fenomenológicos de Judd-Ofelt, &#937&#955 (&#955 = 2, 4, 6), com os quais se calculou as probabilidades de transição radiativa do íon, bem como se verificou o caráter covalente das ligações presentes na matriz. As medidas de Fotoluminescência mostraram que o aumento da concentração de dopante diminui a intensidade da emissão, e que a diminuição da temperatura provoca um aumento da intensidade das mesmas bem como promove o estreitamento das bandas de emissão. Além disto, foi possível verificar a dependência da intensidade da emissão com a energia de excitação utilizada. Para as medidas de Fotoluminescência em baixas temperaturas foi desenvolvido um sistema alternativo baseado numa sonda de fibra óptica cuja utilização mostrou-se mais simples que a tradicional montagem com criostato. / This work presentes the study of the spectroscopic properties of Lead Oxifluroborate Glasses, 40PbO-10PbF2-50B2O3 doped with four different concentrations of Dy3+: 1, 3, 5 e 7 mol%. In order to achieve this, X-ray diffraction, Raman scaterring, Optical absorption, and Photoluminescence techniques were applied. Important parameters like the glass transition temperature, the index of refraction, and the density were also obtained. The behavior of these parameters suggested a possible structural change induced by adding Dy3+: which was confirmed by Raman scattering. The Judd-Ofelt phenomenological parameters, &#937&#955 (&#955 = 2, 4, 6), were calculated from the optical absorption results. From these values the ion radioactive transition probability were obtained and the covalent character of the bonds in the matrix was established. The photoluminescence measurements showed that an increase of Dy3+: concentration diminishes the emission intensity. The opposite happens decreasing the temperature, which also narrows the emission bands. Additionally, the emission intensity dependence with the excitation energy was verified. In order to study photoluminescence in the low temperatures range it was developed an alternative system based on an optical fiber probe. This device revealed to be more simple to operate than cryostat traditional system.

Malgré l'attention massive que le graphène a attiré ces dernières années, beaucoup de questions concernant ses propriétés fondamentales restent sans réponse. Dans ce travail, nous présentons les résultats d'une série d'expériences de magnéto-optique effectuées sur des systèmes de type graphène différents. La spectroscopie de diffusion micro-Raman a été utilisée comme une méthode de choix, en raison de son caractère non invasif, des puissantes possibilités de caractérisation qu’elle offre, et de la haute résolution spatiale. Les champs magnétiques élevés ont aussi été utilisés pour permettre d’ajuster de manière continue l'énergie des excitations électroniques inter-niveau de Landau et de les amener en résonance avec d'autres excitations existant dans le système. L’étude de l'évolution des excitations inter-niveau de Landau sous champs magnétique et les détails de la résonance magnéto-phonon, nous ont fourni des informations importantes sur les détails de l'interaction électron-phonon dans le graphène. Trois types de graphène différents sont étudiés dans ce manuscrit. Le premier se compose de flocons de graphène qui peuvent être trouvés sur la surface de graphite. Il est peut-être le système de graphène le moins étudié, mais est celui qui présente la qualité électronique la plus élevé. Dans le chapitre 7, nous présentons les résultats de nos expériences de diffusion magnéto-Raman sur ce système. Notre méthode de localisation de ces flocons à l'aide ou non d'un champ magnétique est présenté. L'évolution des excitations électroniques dans des champs magnétiques est discutée. Les effets de la température, la longueur d'onde d'excitation et de couplage différent sur le substrat sont présentés. Nous démontrons que, pour des champs magnétiques élevés une structure fine des principales excitations électroniques inter-bande se développe, et est discutée en termes de dopage et d’asymétrie électron-trou. Un nouveau type de résonance électron-phonon est observée, qui implique une diffusion inter-vallée des porteurs et l’émission d'un phonon au point K. Un procédé analogue pour les phonons du voisinage du point Γ est observé. Le deuxième système étudié est constitué d'un flocon de graphène encapsulé entre deux couches de nitrure de bore hexagonal (hBN) plat à l’échelle atomique. Il est le représentant d'une nouvelle classe de matériaux, où les différents cristaux 2D, sont empilés les uns sur les autres dans un ordre prédéfini, pour modifier certaines propriétés de ses constituants. Déposer le graphène sur une mince couche de hBN améliore largement ses propriétés électroniques, en comparaison à du graphène déposée sur Si/SiO2. Dans le chapitre 8, nous présentons des résultats obtenus sur ce système. Nous montrons comment la cartographie spatiale associée à la technique de spectroscopie Raman peut être utilisé pour la caractérisation et la visualisation sélective des composants individuels et des structures complexes empilés. La première observation non ambiguë de la résonance magnéto-phonon et d’une excitation électronique (L -1,1) dans du graphene exfolié neutre est présentée. Une dépendance de la vitesse de Fermi par rapport au champ magnétique est démontrée. En outre, la dépendance de la vitesse de Fermi et d’énergie de bande 2D sur le substrat est observée et discutée en termes de d’écrantage diélectrique de l'interaction électron-électron.Le dernier système étudié sont des flocons de graphène produit par croissance CVD, avec des contacts électriques. Dans le chapitre 9, nous détaillons les résultats d'une expérience, où la force de l'interaction électron-phonon dans un échantillon de graphène avec une grille électrostatique, peut être ajustée, avec succès, par la tension de grille appliquée. Nous comparons ces résultats avec les calculs théoriques et nous montrons que les excitations électroniques intra-bande jouent un rôle important dans la renormalisation de l'énergie des phonons. / Despite the massive attention that graphene has attracted in recent years, there are still many unanswered questions about its fundamental properties. In this work we present the results of a series of magneto-optical experiments performed on different graphene systems. The micro-Raman scattering spectroscopy was used as our method of choice, due to its non-invasive character, powerful characterization possibilities and high spatial resolution. The high magnetic fields were used to continuously tune the energy of inter-Landau level electronic excitations into a resonance with other excitations existing in the system. The magnetic field evolution of Raman active inter-Landau level excitations, and the details of the magneto-phonon resonance, gave us important information about the details of the electron-phonon interaction in graphene. Three different types of graphene are studied in this work. The first one consists of graphene flakes that can be found on the surface of graphite. It is possibly the least investigated graphene system, yet the one that shows the highest electronic quality. In Chapter 7 we present results of our magneto-Raman scattering experiments on this system. Our method for locating these flakes with the use of the magnetic field and without it is presented. The evolution of electronic excitations in magnetic fields is discussed. The effects of temperature, excitation wavelength and different coupling to the substrate are shown. We demonstrate that at high magnetic fields a fine-structure of the principal interband electronic excitation develops and discuss it in terms of doping and electron-hole asymmetry. A new type of a resonant electron-phonon interaction is observed, which involve an inter-valley carrier scattering and an emission of a K-point phonon. An analogous process for the phonons from the vicinity of the Γ point is observed.The second studied system consists of a graphene flake encapsulated between two layers of atomically flat hexagonal boron nitride (hBN). It is a representative of a novel class of materials, where different 2D crystals, are stacked on top of each other in a predefined order, to modify some properties of its constituents. Depositing graphene on a thin layer of hBN is expected to largely improve its electronic properties, as compared to graphene deposited on Si/SiO2. In Chapter 8 we present results obtained on such system. We show how spatial mapping with Raman scattering technique can be used for characterization and selective visualization of each constituent of the complex, stacked structures. A first, clear observation of a magneto-phonon resonance and L(-1,1) electronic excitation in an intrinsic, exfoliated graphene is shown. The Fermi velocity dependence on the magnetic field is demonstrated. Also, the Fermi velocity and 2D band energy dependence on the substrate is observed and discussed in terms of dielectric screening of the electron-electron interaction.The last studied system is the CVD grown graphene flake with electrical contacts. In Chapter 9 we show the results of an experiment, where strength of the electron-phonon interaction in a gated, CVD grown, graphene was successfully tuned by the applied gate voltage. We compare these results with the theoretical calculations and show that the intra-band electronic excitations play an important role in the renormalization of the phonon energy.

INTRODUCTION: The“vulnerable plaque" is defined as the“precursor lesion" that ultimately ends in acute coronary thrombi (clots) that create a heart attack. Macrophages and inflammatory cells, found preferentially in vulnerable plaque, sustain their activity in the plaque through anaerobic metabolism and lactate production. The ultimate goal is to assess anaerobic metabolism in-vivo by measuring tissue pH and lactate concentration in atherosclerotic plaques using optical spectroscopy. The proposed in-vitro optical probe design, experimental method, and spectroscopic data analysis methodology are established in this research. METHODS: A fiber optic probe was designed and built based on both Monte Carlo simulations and bench testing with the goal to collect light from a small volume of tissue. A simulation of the depth penetration of the proposed probe was performed on normal and atherosclerotic aortic tissue, and the final probe was bench tested using normal aorta. A method was developed to preserve plaque metabolic status of tissue harvested from patients. Human atherosclerotic tissue obtained immediately after carotid endarterectomy was placed in Minimum Essential Medium (MEM) with non-essential amino acids supplement, bubbled with 75%O2/20%N2/5%CO2 at 37°C. Tissue pH, pCO2, pO2 and temperature with (n=7) and without (n=2) the media preparation over time were reviewed to assess plaque viability and maintenance of physiological conditions. Additional plaques placed in media were used for development of chemometric methods to measure pH and lactate. Areas of each plaque were randomly chosen for analysis. Reflectance spectra were collected with a dispersive spectrometer (400-1100 nm) and a Fourier-transform near-infrared spectrometer (1100-2400 nm) using the fiber optic probe. Reference measurements for tissue pH and lactate were made with glass microelectrodes and micro-enzymatic assay, respectively. Partial least-squares (PLS) data analysis was used to develop multivariate calibration models on an initial set of 5-6 plaques relating the optical spectra to the reference tissue pH (n=20) or the lactate concentration (n=21) to assess data quality. The coefficient of multiple determination (R2), the standard error of cross-validation (SECV), and the number of factors were used to assess the model performance. Additional points were collected from ~14 plaques and added to preliminary data. Pre-processing techniques were then used to see if preliminary data results could be improved by reducing different sources of variability with the introduction of more points. RESULTS: Monte Carlo simulations and depth penetration tests with the final probe design showed light is collected from ~1 mm3 volume of tissue using a 50 micron source-receiver separation. Tissue pH, pCO2, pO2 and temperature values demonstrated that the plaques were viable and stable in the media preparation for a maximum of 4 hours. Data from the first six plaques collected for lactate analysis showed that for seventeen points, a six-factor model produced adequate results (R2=0.83 SECV=1.4 micromoles lactate/gram tissue). Data from the first five plaques collected for tissue pH analysis, showed for seventeen different points, a three-factor model produced adequate results (R2=0.75 SECV=0.09 pH units). When additional points were added to either data set, model results were degraded. CONCLUSIONS: The in-vitro optical probe design and experimental procedures was established and the feasibility of the optical method demonstrated with preliminary data. However, with the addition of more data points, different sources of tissue and spectral variability were observed to affect calibration. The gross pathology type and mismatched optical volume to reference measurement volume limited the tissue pH determination. The reference measurement precision, the spatial resolution of the reference lactate measurement, and unmodeled tissue variability (water and proteins) limited the lactate determination. Large variability in all optical measurements was observed. Additional in-vitro data collection would be required such that the variability due to the tissue is reduced and any spectrometer variability adequately compensated to be able to use the optical calibration in-vivo.

L’étude intitulée « optical properties of thin layers of transition metal dichalcogenides » vise les phénomènes physiques émergeant à la limite de la bidimensionnalité, lorsque l’épaisseur du composé ciblé est à l’échelle atomique. Les effets de la dimensionnalité réduite sur les propriétés physiques furent initialement explorés dans le graphène. Les études concernant ce composé se concentrent surtout sur ses propriétés de transport puisque le graphène lui-même n’a pas bande interdite. Les sc-TMD, en plus de présenter une structure atomique et électronique similaire au graphène (vallée aux points K dans la zone de Brillouin), peuvent également être produit sous forme de couche monoatomique. Ainsi, plusieurs études révélèrent que ces composés en couche mince combinent des propriétés découlant de leur caractère 2D en plus des caractéristiques typiques des semi-conducteurs. De plus, la dimensionnalité de ces composés joue un rôle important dans la structure électronique. Plus précisément, les sc-TMD présentent dans le régime tridimensionnel un gap indirect qui devient direct lorsque les composés sont sous la forme d’une monocouche. Cette thèse est une étude complète des propriétés optiques des composés sc-TMD. Le manuscrit en question est divisé en cinq parties : trois sections principales précédées par une introduction. L’ensemble est complété par une annexe présentant des études complémentaires sur un autre composé 2D : le nitrure de bore hexagonal (h-BN).Introduction :Les propriétés fondamentales des composés étudiés sont présentées en mettant l’accent sur celles qui jouent un rôle important dans la réponse optique de sc-TMD. Plus précisément, on y retrouve des informations sur la structure cristalline et la structure de bandes électroniques. Cette section détaille également le processus de préparation des échantillons ainsi que les divers montages expérimentaux utilisés.Chapitre 1 : caractérisation optique de base des excitons en résonance dans les couches et les multicouches de sc-TMD.La réponse optique des composés (surtout le MoSe2 et le WSe2) obtenue par spectroscopie de réflexion et par spectroscopie d’émission est interprétée. En particulier, l’impact du nombre de monocouches et de la température sur celle-ci est discuté. De plus, une étude complémentaire de ces propriétés optiques résolue temporellement y est insérée.Chapitre 2 : Spectroscopie Zeeman des excitons résonants sous champ magnétique.L’évolution des résonances optiques en fonction d’un champ magnétique appliqué perpendiculairement aux couches est l’objet de cette section. Un modèle phénoménologique décrivant la dépendance en champs magnétique de l’énergie des états électroniques est dérivé directement des résultats expérimentaux présentés dans cette section. L’effet de pompage optique est également étudié dans la monocouche de WSe2, effet qui est très sensible aux champs magnétiques.Chapitre 3 : Émetteurs de photons uniques dans les couches minces de sc-TMD.La découverte de raies d’émission fines et localisées sur de minces cristallites de sc-TMD est présentée, suivie d’une étude approfondie sur leur nature et leurs propriétés. Entre autres, leur évolution en fonction de la température, leur sensibilité aux champs magnétiques appliqués et leur polarisation sont discutées. Finalement, la spectroscopie de corrélation de photon est utilisée pour vérifier le caractère « source de photon unique » de ces émetteurs.Annexe A : Émetteurs de photons uniques dans le nitrure de bore hexagonal.Le h-BN partage de nombreuses caractéristiques avec les sc-TMD tout en se distinguant de ceux-ci par la présence d’un gap électronique significativement plus grand. Certaines régions cristallines se comportent comme des défauts ponctuels, dans les matériaux caractérisés par leur large gap, en présentant des raies d’émission fines. Ces régions partagent une similarité frappante avec les émetteurs de photons uniques observés dans le WSe2. / The research reported in the thesis entitled ‘Optical properties of thin layers of transition metal dichalcogenides’ focuses on physical phenomena which emerge in the limit of two-dimensional (2D) miniaturisation when the thickness of fabricated films reaches an atomic scale. The importance of such man-made structures has been revealed by the dynamic research on graphene: a single atomic plane of carbon atoms arranged in honeycomb lattice. Graphene is intrinsically gapless and therefore mainly explored with respect to its electric properties. The investigation of semiconducting materials which can also display the hexagonal crustal structure and which can be thinned down to individual layers, bridges the concepts characteristic of graphene-like systems (K-valley physics) with more conventional properties of semiconductors. This has been indeed demonstrated in a number of recent studies of ultra-thin films of semiconducting transition metal dichalcogenides (sc-TMD). Particularly appealing, from the point of view of optical studies, is a transformation of the bandgap alignment of sc-TMD films, from the indirect bandgap bulk crystals to the direct bandgap system in single layers. The presented thesis work provides a comprehensive optical characterisation of thin structures of sc-TMD crystals. The manuscript is divided into five parts: three main chapters with a preceding introduction and the appendix reporting the supplementary studies of another layered material: hexagonal boron nitride.Introduction. The fundamental properties of the investigated crystals are presented, especially those which are important from the point of view of optical studies. The discussion includes information on the crystal structure, Brillouin zone and electronic band structure. Also, the general description of the samples’ preparation process and experimental set-up is provided.Chapter 1. Basic optical characterisation of excitonic resonances in mono- and multi-layers of sc-TMDs. The optical response, as seen in the reflectance and luminescence spectra of thin sc-TMDs is analysed (mostly for MoSe2 and WSe2 materials). The impact of the number of layers and temperature on the optical resonances is studied and interpreted in details. The complementary time-resolved study is also presented.Chapter 2. Zeeman spectroscopy of excitonic resonances in magnetic fields. The evolution of the optical resonances in an external magnetic field, applied perpendicularly to the layers of sc-TMD materials is investigated. Based on these results, a phenomenological model is developed aiming to describe the linear with magnetic field contributions to the energy of individual electronic states in fundamental sub-bands of sc-TMD monolayers. Furthermore, the effects of optical pumping are investigated in WSe2 monolayers, which can be tuned by tiny magnetic fields.Chapter 3. Single photon sources in thin sc-TMD flakes. The discovery of localised narrow lines emitting centres has been in thin sc-TMD flakes is presented. An investigation of their fundamental properties is discussed. This includes the measurements of temperature and magnetic field evolution of the photoluminescence lines, and the analysis of the polarisation properties and the excitation spectra as well as photon correlation measurements.Appendix A. Single photon emitters in boron nitride crystals. Hexagonal boron nitride also belongs to the family of layered materials, but it exhibits much larger band gap than semiconducting transition metal dichalcogenides. A narrow lines emitting centres has been observed in boron nitride structures, which reveal multiple similarities to defect centres in wide gap materials. They are characterised in a similar manner as the emitting centres in WSe2.

Os nitretos do grupo III (AlN, GaN, InN) sao semicondutores extremamente importantes na atualidade principalmente por suas aplicacoes em dispositivos emissores de luz de alta eficiência no visível e no ultravioleta. Neste trabalho foram estudados filmes finos de nitreto de gálio cubico (c-GaN, zincblende) crescidos sobre substratos de carbeto de silício cubico (3C-SiC) por epitaxia de feixe molecular assistida por plasma (PA-MBE). Inicialmente analisou-se o processo de implantação iônica através de técnicas de simulação computacional. Tendo em vista os resultados obtidos pelas simulações, as amostras foram submetidas a processo de implantação iônica com energia de feixe de 200 keV e diferentes íons implantados (Fe, Mn e Cu) nas doses de 1.2 e 2.4 × 1016 cm2. Com a implantação de íons magnéticos buscou-se a criação de um semicondutor com resposta ferromagnética acima da temperatura ambiente, enquanto que com a implantação do íons não magnéticos buscou-se, principalmente, um maior entendimento sobre a influencia de defeitos da rede cristalina sobre o magnetismo do material. Posteriormente as implantações e com o intuito de recuperar a rede cristalina das amostras danificada pelo processo, as amostras foram submetidas a tratamento térmico. Apos cada um destes processos as amostras foram caracterizadas estruturalmente, através de medidas de difração de raios x, espectroscopia de fotoluminescência e espectroscopia Raman e também magneticamente utilizando-se um SQUID. Conseguiu-se a caracterizacao quantitativa das transformações da rede cristalina pre e pós tratamento térmico com as diferentes técnicas. Foi observado comportamento ferromagnético a temperatura ambiente em amostras dopadas com os diversos íons e notou-se uma grande influencia da dose implantada, tanto nas propriedades estruturais quanto magnéticas das amostras. / Group-III nitrides (AlN, GaN, InN) are presently very important semiconductors mainly because of applications in high-efficiency, visible and ultraviolet, light-emitting devices. In this work, thin films of cubic gallium nitride (c-GaN, zincblende), grown over cubic silicon carbide (3C-SiC) by plasmaassisted molecular beam epitaxy (PA-MBE) were studied. Initially the process of ion implantation was investigated with the aid of computer simulation software. Following the simulations results, the samples were implanted with a 200 keV ion-beam of three different ions (Fe, Mn and Cu) with doses of 1.2 and 2.4 × 1016 cm2. With the implantation of magnetic ions the formation of a semiconductor with room-temperature ferromagnetic response was expected, whereas the implantation of non-magnetic ions (Cu) was performed seeking a better understanding on the influence of lattice defects on the subsequent magnetism. After the implantation the samples were annealed to recover some of the crystallinity lost due to the implantation process. After each process the samples were structurally characterized through x-ray diffraction, photoluminescence and Raman spectroscopies, and magnetically characterized through SQUID magnetometry. A quantitative measure of the transformations of the crystal lattices was obtained before and after annealing with the different techniques. Room-temperature ferromagnetic behavior was observed in the samples doped with different ions and a large influence of implanted dose was noted, in the structural properties and also in the magnetic properties.

Current micro-scale electronics technology has been approaching rapidly towards its technological limit. This has shifted the focus towards nano-scale technology in recent years. More and more researchers around the globe are working in pursuit of bringing nano-scale technology into mainstream. The research carried out here is a small step towards a similar goal. The remarkable optical properties exhibited by certain nano-scale structures are in stark contrast to their bulk form and this provides the basis for this research. Two kinds of nanostructures are developed and investigated for their optical properties. One of these is nanofibers processed from a polymer known as polyaniline (PANI). The focus of this study is to investigate its optical and conductive properties under different conditions of doping environments, temperature and polymerization conditions. Optical characterization technique such as UV-Visible spectroscopy is developed to carry out the investigation. The developed nanofibers have been demonstrated to possess optical and conductive properties to be dependent on doping variables. Study of these optical properties could prove very useful in the development of electrochromic devices and gas sensors. Later in the research, UV-Visible spectroscopy has been improved into a low cost Raman spectroscopy setup which is validated by experimentation carried out on some samples. The second type of nano-structure developed and investigated, is an array of nanoparticles of noble metals such as gold and silver. Such an array is shown to exhibit a phenomenon called plasmon resonance effect when excited by light. UV-Visible spectroscopy technique is utilized to investigate this effect for metal nano-arrays. A biologically nano-structured surface (wing of an insect called cicada) is used as the substrate for the fabrication of metal array. A serious attempt has also been made to do 'Surface Enhanced Raman Spectroscopy (SERS)', making use of the metal nano-array developed. This technique improves the raman lines intensities of certain less sensitive samples such as thiophenol, which are known to give weak raman lines. This is carried out by adsorbing the sample on the metal nano-array.

Relative changes are detectable in the blood of end-stage renal disease (ESRD) patients during hemodialysis (HD) treatment using optical spectroscopy. However, the potential impacts of several confounding factors that could affect the detection of these changes have not been evaluated. The objectives of this thesis were to: 1) investigate how the variations and/or changes in acid-base and oxygen parameters during HD treatment can affect the optical signature of whole blood of ESRD patients, 2) to investigate the effect of heparin on the optical properties of whole blood and its impact on our method. Blood samples were drawn from 23 ESRD patients at 5 time points during a 4 hour HD treatment and sent for blood gas and blood spectroscopy analyses. No significant correlations were found between the changes in the blood transmittance spectra and acid-base and oxygen parameters. This indicates that the perturbations in these parameters due to HD procedures do not confound the detection of changes in the blood transmittance spectra of ESRD patients during HD treatment. Additionally, the effect of heparin in modifying the optical properties of whole blood does not confound the detection of changes in the blood of ESRD patients due to HD treatment using whole blood-based optical spectroscopy. ANOVA revealed significant (P<0.05) measurable changes in the blood transmittance spectra of ESRD patients during HD treatment. Significant spectral differences (P<0.05) were found between ESRD patients. The lack of uniform spectral characteristics across patients is

The clinical management of glioma remains a challenge. The prognosis is poor—for glioblastoma multiforme, the most virulent of these brain cancers, survival is only ~1 year. Surgical resection of the tumor is the first line of defense. Several studies demonstrate a survival advantage in patients who undergo near-complete tumor resection; however, achieving complete resection is limited by the difficulty of visualizing residual tumor after de-bulking. Intraoperative fluorescence guidance is a promising candidate to better visualize residual tumor. The most clinically developed form uses protoporphyrin IX fluorescence, the precursor to heme in its biosynthesis which preferentially accumulates in tumor cells after the administration of 5-aminolevulinic acid. Challenges remain in quantitatively assessing the fluorescence to reduce variability of outcome and improve tumor detection specificity, and in observing sub-surface tumor fluorescence. To these ends, this work outlines the development of intraoperative techniques to 1) quantify tissue fluorescence using a handheld fiberoptic probe and 2) improve detection by reconstructing the depth-resolved fluorescence topography of sub-surface tumor. As a critical component to achieve these objectives, a technique to measure the tissue optical properties was developed. This technique used diffuse reflectance measurements mediated by a handheld fiberoptic probe to derive the tissue optical properties. The handheld fiberoptic probe was further developed to include fluorescence spectroscopy. A novel algorithm to combine the fluorescence measurement and the tissue optical properties was derived in order to extract the quantitative fluorescence spectrum, i.e. fluorescence without confounding effects of tissue optical properties. The concentration of fluorescent tumor biomarker can then be extracted. The quantitative fluorescence work culminated in deployment of the fiberoptic probe in clinical trials for the resection of intracranial tumors. The quantitative fluorescence probe out-performed a state-of-the-art fluorescence surgical microscope for a broad range of brain tumor pathologies. A novel technique for depth-resolved fluorescence detection was developed utilizing multi-excitation fluorescence imaging. An algorithm to extract depth information from the multi-excitation images was derived, with validation in phantoms and a rat brain tumor model. This demonstrates the potential for depth-resolved fluorescence imaging, which there is a clear need for in tumor resection guidance.

The clinical management of glioma remains a challenge. The prognosis is poor—for glioblastoma multiforme, the most virulent of these brain cancers, survival is only ~1 year. Surgical resection of the tumor is the first line of defense. Several studies demonstrate a survival advantage in patients who undergo near-complete tumor resection; however, achieving complete resection is limited by the difficulty of visualizing residual tumor after de-bulking. Intraoperative fluorescence guidance is a promising candidate to better visualize residual tumor. The most clinically developed form uses protoporphyrin IX fluorescence, the precursor to heme in its biosynthesis which preferentially accumulates in tumor cells after the administration of 5-aminolevulinic acid. Challenges remain in quantitatively assessing the fluorescence to reduce variability of outcome and improve tumor detection specificity, and in observing sub-surface tumor fluorescence. To these ends, this work outlines the development of intraoperative techniques to 1) quantify tissue fluorescence using a handheld fiberoptic probe and 2) improve detection by reconstructing the depth-resolved fluorescence topography of sub-surface tumor. As a critical component to achieve these objectives, a technique to measure the tissue optical properties was developed. This technique used diffuse reflectance measurements mediated by a handheld fiberoptic probe to derive the tissue optical properties. The handheld fiberoptic probe was further developed to include fluorescence spectroscopy. A novel algorithm to combine the fluorescence measurement and the tissue optical properties was derived in order to extract the quantitative fluorescence spectrum, i.e. fluorescence without confounding effects of tissue optical properties. The concentration of fluorescent tumor biomarker can then be extracted. The quantitative fluorescence work culminated in deployment of the fiberoptic probe in clinical trials for the resection of intracranial tumors. The quantitative fluorescence probe out-performed a state-of-the-art fluorescence surgical microscope for a broad range of brain tumor pathologies. A novel technique for depth-resolved fluorescence detection was developed utilizing multi-excitation fluorescence imaging. An algorithm to extract depth information from the multi-excitation images was derived, with validation in phantoms and a rat brain tumor model. This demonstrates the potential for depth-resolved fluorescence imaging, which there is a clear need for in tumor resection guidance.

Relative changes are detectable in the blood of end-stage renal disease (ESRD) patients during hemodialysis (HD) treatment using optical spectroscopy. However, the potential impacts of several confounding factors that could affect the detection of these changes have not been evaluated. The objectives of this thesis were to: 1) investigate how the variations and/or changes in acid-base and oxygen parameters during HD treatment can affect the optical signature of whole blood of ESRD patients, 2) to investigate the effect of heparin on the optical properties of whole blood and its impact on our method. Blood samples were drawn from 23 ESRD patients at 5 time points during a 4 hour HD treatment and sent for blood gas and blood spectroscopy analyses. No significant correlations were found between the changes in the blood transmittance spectra and acid-base and oxygen parameters. This indicates that the perturbations in these parameters due to HD procedures do not confound the detection of changes in the blood transmittance spectra of ESRD patients during HD treatment. Additionally, the effect of heparin in modifying the optical properties of whole blood does not confound the detection of changes in the blood of ESRD patients due to HD treatment using whole blood-based optical spectroscopy. ANOVA revealed significant (P<0.05) measurable changes in the blood transmittance spectra of ESRD patients during HD treatment. Significant spectral differences (P<0.05) were found between ESRD patients. The lack of uniform spectral characteristics across patients is