Fluorescence diffuse optical tomography provides non-invasive, in vivo imaging of molecular targets in small animals. While standard fluorescence microscopy is limited to shallow depths and small fields of view, tomographic methods allows recovery of the distribution of fluorescent probes throughout the small animal body. In this thesis, we present novel reconstruction algorithms for the tomographic separation of optical parameters using time-domain (TD) measurements. These technique are validated using simulations and with experimental phantom and mouse imaging studies. We outline the contributions of each chapter of the thesis below. First, we explore the TD fluorescence tomography reconstruction problem for single and multiple fluorophores with discrete lifetimes. We focus on late arriving photons and compare a direct inversion approach with a two-step, asymptotic approach operating on the same TD data. We show that for lifetime multiplexing, the two methods produce fundamentally different kinds of solutions. The direct inversion is computationally inefficient and results in poor separation but has overall higher resolution while the asymptotic approach provides better separation, relative quantitation of lifetime components and localization but has overall lower resolution. We verify these results with simulation and experimental phantoms. Second, we introduce novel high resolution lifetime multiplexing algorithms which combine asymptotic methods for separation of fluorophores with the high resolving power of early photon tomography. We show the effectiveness of such methods to achieve high resolution reconstructions of multiple fluorophores in simulations with complex-shaped phantoms, a digital mouse atlas and also experimentally in fluorescent tube phantoms. Third, we compare the performance of tomographic spectral and lifetime multiplexing. We show that both of these techniques involve a two-step procedure, consisting of a diffuse propagation step and a basis-function mixing step. However, in these two techniques, the order of the two steps is switched, which leads to a fundamental difference in imaging performance. As an illustration of this difference, we show that the relative concentrations of three colocalized fluorophores in a diffuse medium can accurately be retrieved with lifetime methods but cannot be retrieved with spectral methods. Fourth, we address the long standing challenge in diffuse optical tomography (DOT) of cross-talk between absorption and scattering. We extend the ideas developed from lifetime multiplexing algorithms by using a constrained optimization approach for separation of absorption and scattering in DOT. Using custom designed phantoms, we demonstrate a novel technique allows better separation of absorption and scattering inclusions compared to existing algorithms for CW and TD diffuse optical tomography. Finally, we show experimental validation of the lifetime multiplexing algorithms developed in this thesis using three experimental models. First, we show the reconstruction of overlapping complex shapes in a dish phantom. Second, we demonstrate the localization accuracy of lifetime based methods using fluorescent pellets embedded in a sacrificed mouse. Third, we show using planar imaging and tomography, the in vivo recovery of multiple anatomically targeted near-infrared fluorophores. In summary, we have presented novel reconstruction algorithms and experimental methods that extend the capability of time-domain fluorescence diffuse optical tomography systems. The methods developed in this thesis should also have applicability for general multi-parameter image reconstruction problems. / Engineering and Applied Sciences

Ultrathin fiberscopes typically have an imaging channel and an illumination channeland are available in diameters ranging from 0.5 mm to 2.5 mm. The minimum diam-eter can be reduced by combining the illumination and imaging paths into a singlefiberoptic channel. Constructing a single channel fiberscope requires a technique ofilluminating the tissue, while minimizing the Fresnel reflections and scatter withinthe common illumination and detection channel.A single channel fiberscope should image diffusely reflected light from tissue illu-minated with light filtered for the visible wavelength range (450 - 650 nm). Simplycombining the illumination and collection paths via a beamsplitter results in a lowobject to background signal ratio. The low contrast image is due to a low collectionefficiency of light from the ob ject as well as a high background signal from the Fresnelreflection at the proximal surface of the fiber bundle, where the illumination enters thefiber bundle. The focus of the dissertation is the investigation of methods to reducethe background signal from the proximal surface of the fiber bundle. Three systemswere tested. The first system uses a coherent fiber bundle with an AR-coating on theproximal face. The second system incorporates crossed polarizers into the light path.In addition, a technique was developed, whereby a portion of the image numericalaperture is devoted to illumination and a portion to image signal detection. Thistechnique is called numerical aperture sharing (NA sharing).This dissertation presents the design, construction, testing, and comparison ofthe three single channel fiberscopes. In addition, preliminary results of a study aimedat the usefulness of broadband diffuse reflectance imaging for the identification andtracking of disease progression in mouse esophagus are presented.

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This investigation evaluates the influences of optical property assumptions on nearinfrared diffuse correlation spectroscopy (DCS) flow index measurements. Independent variation is induced in optical properties, absorption coefficient (μa) and reduced scattering coefficient (μs’), of liquid phantoms with concurrent measurements of flow indices. A hybrid instrument is incorporated consisting of a dual-wavelength (785 and 830 nm) DCS flow device to obtain flow indices and a frequency-domain tissue-oximeter for optical properties. Flow indices are calculated with measured μa and μs’ or assumed constant μa and μs’. Inaccurate μs’ assumptions produced much larger flow index errors than inaccurate μa. Underestimated/overestimated μs’ from -35%/+175% lead to flow index errors of +110%/-80% and underestimated/overestimated μa from -40%/+150% lead to -20%/+40%, regardless of wavelength. Analysis of a clinical study involving human head and neck tumors indicates flow index errors due to inter-patient optical property variations up to +280%. Collectively, these findings suggest that studies involving significant μa and μs’ changes should measure flow index and optical properties simultaneously to accurately extract blood flow information. This study provides unique insight through the use of liquid phantoms, hybrid instrumentation, incorporation of measurement errors and a generalization into DCS flow index errors due to the influences of optical properties.

L'assistance aux personnes ayant des troubles cognitifs, au laboratoire DOMUS, se fait selon deux approches. La première met en oeuvre des outils d'assistance personnelle portés par la personne, comme le panic button ou encore une application déployée sur un téléphone intelligent. La seconde consiste à équiper l'environnement de la personne afin de lui proposer une aide discrète qui ne modifie que très peu ses habitudes de vie. Ce présent projet de recherche s'inscrit dans la seconde approche d'assistance. Ce mémoire a pour but de proposer un prototype de sol intelligent permettant la localisation et même l'identification des personnes présentes dans un espace intelligent. Les sols intelligents jusqu'alors développés présentent tous la même particularité : ils nécessitent, pour les déployer et les exploiter, des connaissances avancées dans les domaines de l'informatique et de l'électronique ainsi que la mise en place d'un processus complexe pour leur déploiement et leur exploitation. L'architecture proposée pour ce prototype de sol intelligent vise à faciliter au maximum sa configuration et son utilisation afin de réduire au maximum les coûts qui y sont liés. Pour faciliter le développement des algorithmes d'auto-configuration et d'exploitation des noeuds constituant le sol intelligent, un simulateur a été réalisé. Il permet de confirmer le comportement de ces algorithmes dans un réseau de grande dimension sans avoir à mettre en place une réalisation matérielle qui représente une étape complexe et coûteuse. La mise en oeuvre, d'un point de vue matériel, au niveau matériel n'a été réalisée que sur un nombre limité de noeuds afin d'en démontrer la faisabilité.

Le Québec vit un vieillissement marqué de sa population et doit faire face aux problèmes que cela engendre. Cette situation soulève des enjeux sociaux et économiques liés à la santé comme l'augmentation des problèmes chroniques de santé en fin de vie, le maintien de la qualité des soins à la population et plus généralement le financement du domaine de la santé. Le Centre de recherche sur les habitats intelligents (CRHI) de l'Université de Sherbrooke cherche à développer une solution technologique socialement acceptable à ces enjeux. Les travaux qui y sont faits visent à favoriser l'autonomie de personnes atteintes de troubles cognitifs afin de leur permettre de demeurer à domicile le plus longtemps possible. Cette recherche doctorale porte spécifiquement sur l'utilisation des technologies de l'habitat intelligent pour soutenir le travail coopératif entre les professionnels de la santé, les intervenants sociaux et les proches aidants. On y aborde la problématique du travail "même lieu/temps différents" dans l'équipe hétérogène sous l'angle du travail coopératif assisté par ordinateur (TCAO). Un collecticiel asynchrone distribué dans l'habitat intelligent a été développé à titre de preuve de concept. Des activités de communication, de coordination et de production des intervenants ont été scénarisées afin de démontrer le fonctionnement du prototype. Le collecticiel C4C intègre notamment des outils de travail éprouvés comme le système de mesure de l'autonomie fonctionnelle (SMAF) qui est utilisé pour déterminer et suivre le niveau de service à offrir à une personne en perte d'autonomie. Notre recherche a permis d'élaborer : - une infrastructure distribuée de services sous l'approche par réseau de pairs pour un habitat intelligent ; - un modèle de gestion de l'information dans une perspective historique et spatiale intérieure tridimensionnelle ; - un modèle de gestion de la coopération en mode "pousser de l'information" basé sur le contexte de travail. Ensemble, ces contributions structurent et définissent le mode de travail dans l'équipe de soins et de maintien à domicile. En facilitant la coopération dans l'habitat intelligent, notre recherche vise la continuité accrue des soins pour permettre à plus de personnes souffrant de limitations cognitives ou physiques de vivre à la maison dans leur communauté.

The mining, agricultural and energy sectors, along with the Department of Water Affairs (DWA) are critical role players in managing South Africa’s water resources. Water resources are under increasing pressure due to continuous population growth and economic development. It is critical to adopt a management policy that can lead to sustainable water supply. The National Water Act, 1998, (Act 36 of 1998), Section 56(1) instructs the Minister of Water Affairs to establish a Pricing Strategy for charges for any water use described in Section 21 of the Act. In light of this the Department implemented the Waste Discharge Charge System (WDCS). The WDCS is based on the polluter-pays principle and is focussed on load reduction on order to achieve or maintain resource quality objectives. One of the legal requirements in the mining industry is to have a water use license under Section 21 of the National Water Act of 1998 (South Africa, 1998b) which will lead to the application of the WDCS to the mining industry. This mini-dissertation assesses how the WDCS can be practically implemented from a gold mining perspective. The WDCS require the identification of point and diffuse sources from various pollution sources. A case study was used to determine what information and instruments will be required at a gold mine to implement the WDCS. The determining of the point and diffuse discharges require multidisciplinary studies with the integration of different spheres of the environment. To assist with this a GoldSim model was developed. The main function of the model was to determine the seepage rates per day from pollution sources using the available information. The seepage rates and the water qualities were used to determine the waste loads discharged to the environment. Using the instruments above, a methodology was provided to determine the point and diffuse sources of pollution and calculate the load that will be discharged to the environment which will form the basis of the WDCS. / Thesis (M. Environmental Management)--North-West University, Potchefstroom Campus, 2013

The mining, agricultural and energy sectors, along with the Department of Water Affairs (DWA) are critical role players in managing South Africa’s water resources. Water resources are under increasing pressure due to continuous population growth and economic development. It is critical to adopt a management policy that can lead to sustainable water supply. The National Water Act, 1998, (Act 36 of 1998), Section 56(1) instructs the Minister of Water Affairs to establish a Pricing Strategy for charges for any water use described in Section 21 of the Act. In light of this the Department implemented the Waste Discharge Charge System (WDCS). The WDCS is based on the polluter-pays principle and is focussed on load reduction on order to achieve or maintain resource quality objectives. One of the legal requirements in the mining industry is to have a water use license under Section 21 of the National Water Act of 1998 (South Africa, 1998b) which will lead to the application of the WDCS to the mining industry. This mini-dissertation assesses how the WDCS can be practically implemented from a gold mining perspective. The WDCS require the identification of point and diffuse sources from various pollution sources. A case study was used to determine what information and instruments will be required at a gold mine to implement the WDCS. The determining of the point and diffuse discharges require multidisciplinary studies with the integration of different spheres of the environment. To assist with this a GoldSim model was developed. The main function of the model was to determine the seepage rates per day from pollution sources using the available information. The seepage rates and the water qualities were used to determine the waste loads discharged to the environment. Using the instruments above, a methodology was provided to determine the point and diffuse sources of pollution and calculate the load that will be discharged to the environment which will form the basis of the WDCS. / Thesis (M. Environmental Management)--North-West University, Potchefstroom Campus, 2013

L’objectif de ce projet de recherche est de développer une technologie d’agents mobiles pour systèmes embarqués. Dans un premier temps, une plateforme d’agents mobiles pour systèmes embarqués homogènes est réalisée et, ensuite dans un deuxième temps, une application d’informatique diffuse qui exploite la mobilité du contexte d’exécution est mise en œuvre pour valider cette plateforme. La mobilité d’un agent est définie comme suit: son exécution est interrompue sur le nœud courant, appelé nœud source, ensuite les données représentant l’état de l’agent sont transférées du nœud source vers un nœud destination et enfin, arrivé au nœud destination, son exécution se poursuit là où elle avait été interrompue sur le nœud de départ. Cette opération, appelée migration du contexte d’exécution, est intégrée aux fonctionnalités d’un noyau temps réel, permettant ainsi la mobilité d’agents logiciels au sein d’une grappe de systèmes embarqués homogènes. Les applications visées par le projet relèvent du domaine de l’informatique diffuse et plus particulièrement de son application à l’espace intelligent.

Prior research suggests aggressive cancer treatments contribute to cognitive impairments in children diagnosed with pediatric brain tumors. The literature also suggests that younger age at diagnosis (AAD) and treatment may result in disrupted cognitive trajectories due to limited brain plasticity. In line with this research, we hypothesized an interaction between radiation therapy (RT) and young AAD of brain tumors, where young AAD and RT results in lower standard scores on the WRAT-R Reading Comprehension Subtest. Analyses included archival data; the sample consists of 134 children diagnosed with pediatric brain tumors with multiple assessments resulting in 487 cases for analysis. Participants were diagnosed with mixed tumor types and locations. A two level multilevel model was used to analyze reading trajectories while taking into account AAD, time since diagnosis, socioeconomic status (SES), and RT. Results detected a positive interaction between AAD and RT (γ =2.08, p=.02). For participants with RT, younger AAD was associated with lower reading scores, whereas AAD had no effect for participants without RT. Results also detected a negative interaction between radiation and time (γ =-2.29, p=.00) indicating that children treated with RT have reading scores that decrease over time. These data suggested that children diagnosed with pediatric brain tumors treated with RT are at higher risk of reading impairment as reflected in their reading scores.