In many medical imaging modalities, as photons travel from the emission source to the detector, they are scattered by the biological tissue. Often this scatter is viewed as a phenomenon that degrades image quality, and most research is focused on designing methods for either discarding the scattered photons or correcting for scatter. However, the scattered photons also carry information about the tissue that they pass through, which can perhaps be extracted. In this research, we investigate methods to retrieve information from the scattered photons in two specific medical imaging modalities: diffuse optical tomography (DOT) and single photon emission computed tomography (SPECT). To model the scattering of photons in biological tissue, we investigate using the Neumann-series form of the radiative transport equation (RTE). Since the scattering phenomenon are different in DOT and SPECT, the models are individually designed for each modality. In the DOT study, we use the developed photon-propagation model to investigate signal detectability in tissue. To study this detectability, we demonstrate the application of a surrogate figure of merit, based on Fisher information, which approximates the Bayesian ideal observer performance. In the SPECT study, our aim is to determine if only the SPECT emission data acquired in list-mode (LM) format, including the scattered-photon data, can be used to compute the tissue-attenuation map. We first propose a path-based formalism to process scattered photon data, and follow it with deriving expressions for the Fisher information that help determine the information content of LM data. We then derive a maximum-likelihood expectation-maximization algorithm that can jointly reconstruct the activity and attenuation map using LM SPECT emission data. While the DOT study can provide a boost in transition of DOT to clinical imaging, the SPECT study will provide insights on whether it is worth exposing the patient to extra X-ray radiation dose in order to obtain an attenuation map. Finally, although the RTE can be used to model light propagation in tissues, it is computationally intensive and therefore time consuming. To increase the speed of computation in the DOT study, we develop software to implement the RTE on parallel computing architectures, specifically the NVIDIA graphics processing units (GPUs).

In the last fifteen years, a great deal of effort has been put forth, worldwide, for investigating and enhancing various aspects of optical coherence tomography (OCT). This thesis begins with a description of the technique of OCT, and an analysis of its underlying theory. The design and construction of an OCT system is described, with particular emphasis on a novel delay scanning method, and novel signal processing. Application of OCT to non-destructive characterisation of seeds, examination of skin lesions, measurement of fluid flow, and refractive index determination, are then demonstrated. Two technological enhancements to OCT are presented in this thesis. The first, an extended-range Fourier domain optical delay line (FDODL), extends the scan range of the traditional FDODL by a factor of almost 9, by scanning the galvanometer mirror around the region of zero tilt-angle. Polarisation optics are used to prevent light coupling back into the interferometer after only a single pass through the FDODL. A non-coplanar version of the FDODL is also presented, which overcomes the losses associated with the polarisation-based design, but trades off scan range to do so. Both versions of FDODL demonstrated excellent linearity and scan uniformity. The second technology presented here, bifocal optical coherence refractometry (BOCR), affords OCT the ability to measure refractive indices within turbid media. It achieves this by generating two confocal gates within the sample. From knowledge of the system parameters, and measurements of the confocal gate separation, the refractive index within the medium is evaluated to within ±0.01. Refractive index mapping is then demonstrated in a number of turbid samples. Three other applications of OCT are also demonstrated in this thesis. The first is the use of OCT to measure full thickness in lupin seeds. Although OCT could not penetrate the entire thickness of the hull, it is demonstrated that the variation in thickness of the two layers observed with OCT, explained 81% of the variation in thickness of the entire hull measured under a SEM. OCT was then applied, for what is believed to be the first time, in a large scale seed screening program. The second application is a preliminary investigation of the suitability of OCT to aid in the diagnosis of skin lesions. Although our system did not possess sufficient positioning accuracy to enable a direct one-to-one comparison between OCT and histology, a number of correspondences between OCT and histology images were demonstrated. The final application of OCT demonstrated here is a novel phase-locked-loop based demodulation scheme, to perform Doppler OCT. This demodulation scheme demonstrated a dynamic range of 98dB, a velocity range of ±20mm/s, and velocity resolution of 0.5mm/s. Using this system, laminar flow was demonstrated in milk flowing through a capillary tube.

[Truncated abstract] This thesis describes the development, clinical validation and initial application of a technique for taking measurements of the shape and dimensions of the human upper airway, called anatomical optical coherence tomography (aOCT). The technique uses a transparent catheter containing a rotating optical probe which is introduced transnasally and positioned in the airway and oesophagus. Optical coherence tomography is used to take calibrated cross-sectional images of the airway lumen as the probe rotates. The probe can also be advanced or withdrawn within the catheter during scanning to build up three-dimensional information. The catheter remains stationary so that the subject is not aware of the probe motion. The initial application of the system is research into obstructive sleep apnoea (OSA), a serious condition characterized by repetitive collapse of the upper airway during sleep and an independent risk factor for deaths by heart disease, strokes or car accidents. Measurement of upper airway size and shape is important for the investigation of the pathophysiology of OSA, and for the development and assesment of new treatments. . . We have used aOCT to capture three-dimensional data sets of the airway shape from upper oesophagus to the nasal cavity, undertaken measurements of compliance and other airway characteristics, and recorded dynamic airway shape during confirmed sleep apnoea events in a hospital sleep laboratory. We have shown that aOCT generates quantitative, real-time measurements of upper airway size and shape, allowing study over lengthy periods during both sleep and wakefulness. These features should make it useful for study of upper airway behavior to investigate OSA pathophysiology, and aid clinical management and treatment development.

La tomographie optique diffuse de fluorescence permet la reconstruction tridimensionnelle de fluorophores présents dans un tissu biologique. La modalité la plus simple de cette technique repose sur une illumination continue du milieu et s'intéresse aux mesures d'atténuation du faisceau incident en différentes positions. En raison de la forte diffusion des tissus, la modalité continue souffre d'une faible résolution en profondeur.On considère aujourd'hui que la modalité résolue en temps, qui fournit pour chaque photon détecté son temps de vol, permettrait l'étude de tissus plus épais, ouvrant ainsi la porte à des applications cliniques. L'objet de cette thèse est de chercher comment tirer profit de l'information temporelle et de quantifier son apport par rapport à la modalité continue.La tomographie optique diffuse de fluorescence est un problème inverse mal conditionné. Dans un contexte où tout écart au modèle doit être limité, nous nous intéressons tout d'abord au modèle direct et montrons que la densité de photons est un modèle satisfaisant de la quantité expérimentalement mesurée. Nous passons ensuite au crible la méthode de reconstruction fondée sur l'exploitation des moments temporels des mesures. Étudiant théoriquement les propriétés des moments, nous montrons que cette approche nécessite, pour s'avérer intéressante, la détection d'un nombre élevé de photons. Nous introduisons enfin une nouvelle approche permettant d'exploiter l'information temporelle pour un nombre de photons plus limité. Cette approche, reposant sur une transformation en ondelettes des mesures, offre une qualité de reconstruction accrue par rapport à celle offerte par l'approche des moments. / Fluorescence diffuse optical tomography enables the three-dimensional reconstruction of fluorescence markers injected within a biological tissue, with light in the near infrared range. The simple continuous modality uses steady excitation light and operates from the measurements at different positions of the attenuation of the incident beam. This technique is low-cost, non-ionizing, and easy to handle, but subject to low resolution for thick tissues due to diffusion. Hopefully, the time-resolved modality, which provides the time of flight of any detected photon, could overcome this limitation and pave the way to clinical applications. This thesis aims at determining the best way to exploit the time resolved information and at quantifying the advantages of this modality over the standard continuous wave one.Model deviations must be carefully limited when ill-posed problems as fluorescence diffuse optical tomography are considered. As a result, we have first addressed the modelling part of the problem. We have shown that the photons density models to good approximation the measurable quantity that is the quantity measured by an actual acquisition set-up. Then, the moment-based reconstruction scheme has been thoroughly evaluated by means of a theoretical analysis of the moments’ properties. It was found that the moment-based approach requires high photon counts to be profitable compared to the continuous wave modality. Last, a novel wavelet-based approach, which enables an improved reconstruction quality, has been introduced. This approach has shown good ability to exploit the temporal information at lower photon counts.

La tomographie optique diffuse (TOD) est une technique d'imagerie médicale émergente utilisant la lumière proche infrarouge pour sonder les tissus biologiques. A partir de mesures non-invasives, cette technique permet d'obtenir les cartes en trois dimensions des coefficients d'absorption et de diffusion à l'intérieur des organes. Avec une approche multi-spectrale, la distribution spatiale des chromophores endogènes (hémoglobine, eau) peut aussi être obtenue. Pour certaines applications cliniques, il est souhaitable d'effectuer les mesures de TOD avec une sonde compacte qui regroupe tous les couples source-détecteur. Cependant, dans cette configuration, la sensibilité en profondeur est un défi majeur. Dans le cadre de cette thèse, nous proposons d'adresser ce challenge en utilisant des mesures résolues en temps. Une approche résolue en temps est développée pour optimiser la TOD dans le cas des mesures de réflectance à faibles distances source-détecteur. Cette approche inclut des aspects méthodologiques concernant le traitement des mesures résolues en temps par des algorithmes de TOD basés sur la transformée de Mellin-Laplace. Cette approche comporte aussi un volet instrumental qui consiste à optimiser la chaîne de détection sur deux points précis pour améliorer la détection et la localisation de contraste d'absorption en profondeur dans les milieux diffusants. Tout d'abord, l'impact de la réponse temporelle du détecteur est étudié avec des détecteurs de photons uniques disponibles dans le commerce (photomultiplicateurs classiques et hybrides). Dans un second temps, l'augmentation de la profondeur sondée avec de nouveaux détecteurs de photons uniques, les fast-gated single-photon avalanche diodes, est explorée au cours d'une collaboration avec le Politecnico de Milan. Pour finir, une étude illustre les performances de l'approche proposée en termes de résolution spatiale en profondeur pour différents arrangements des sources et détecteurs dans une sonde optique. Des sondes optiques dont la largeur est limitée à quelques centimètres ouvrent la voie à de nouvelles applications cliniques pour la TOD. Ces sondes peuvent accéder à des organes internes comme la prostate ou faciliter les examens médicaux sur des organes externes comme le sein ou le cerveau. / Diffuse optical tomography (DOT) is an emerging medical imaging technique using near-infrared light to probe biological tissues. This technique can retrieve three-dimensional maps of absorption and scattering coefficients inside organs from non-invasive measurements. With a multispectral approach, the spatial distribution of endogenous chromophores (hemoglobin, water) can even be obtained. For some clinical applications, it is desirable to carry out the measurements for DOT with a compact probe including all sources and detectors. However, the depth sensitivity is a real challenge in this configuration. We propose to tackle this challenge by using time-resolved measurements. A time-resolved approach is developed to perform DOT with reflectance measurements at short source-detector separation. This approach involves methodological aspects including the processing of time-resolved signals by DOT algorithms based on the Mellin-Laplace transform. Then, this approach consists in optimizing the detection chain on two aspects for enhancing the detection and localization of absorption contrast in depth in diffusive media. First, the impact of the temporal response of the detector is studied with commercially available single-photon detectors (classical and hybrid photomultipliers). Second, the enhancements in probed depth permitted with fast-gated single-photon avalanche diodes are explored in a joint work with the Politecnico di Milano. To finish, a study is carried out to illustrate the performance of the proposed approach with respect to spatial resolution in depth for different configurations of sources and detectors in the optical probe. Probes with a width limited to a few centimeters open the gate to multiple clinical interests. They could access intern organs like the prostate or facilitate the measurements on extern organs like the breast or the brain.

Made available in DSpace on 2014-10-09T12:42:21Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:02:11Z (GMT). No. of bitstreams: 0 / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Tese (Doutoramento) / IPEN/T / Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP / FAPESP:09/13764-3

Made available in DSpace on 2014-10-09T12:42:21Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:02:11Z (GMT). No. of bitstreams: 0 / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Tomografia por Coerência Óptica, ou simplesmente OCT (acrônimo do inglês: Optical Coherence Tomography), é uma técnica para geração de imagens de seções transversais de meios espalhadores ao comprimento de onda utilizado. A OCT é baseada em interferometria óptica e gera imagens comumente correlacionadas às imagens geradas exames histológicos com a vantagem de ser indolor, não invasiva e não utilizar radiação ionizante. Este estudo dividiu-se em dois objetivos distintos, um refere-se à aplicação de sinais interferométricos de autocorrelação para a formação de imagens de amostras com estruturas complexas. O segundo objetivo foi o estudo das estruturas denominadas de harmônicos e sua aplicação no aumento da resolução axial de um sistema OCT. Com relação à primeira parte, constatou-se que o sinal interferométrico de autocorrelação é muitas vezes ignorado ou descartado pela OCT tradicional. Análises mais profundas da teoria de interferometria, juntamente com alguns estudos anteriores, apontaram para a possibilidade de gerar imagens de maior complexidade morfológica utilizando o sinal de autocorrelação, com a vantagem de se utilizar um arranjo óptico mais simples e também possibilitar imagens estáticas de amostras em movimento axial. Para testar os benefícios e as limitações da técnica de autocorrelação (Au-OCT) foi montado em laboratório e foram realizadas imagens de amostras no repouso e em movimento e confrontadas com imagens geradas no sistema OCT convencional. O sistema de Au-OCT foi capaz de gerar imagens de estruturas diversas (dentes, filmes plásticos entre outros), e apesar de possuir uma qualidade de imagem inferior à OCT, ela apresentou vantagens quando a amostra sofre deslocamentos axiais. Já em relação as características harmônicas, que se apresentam em amostras de alta refletividade óptica como falsas estruturas em imagens OCT, todo um estudo para o entendimento do fenômeno foi desenvolvido. Demonstrou-se também a possibilidade de utilização dessas estruturas para aprimorar a resolução axial diferencial (entre estruturas da própria amostra) através de um estudo numérico e experimental. Para isso padrões dimensionais do tipo degrau foram mensurados e os resultados tratados de acordo com procedimentos metrológicos, mostrando que os harmônicos podem ser utilizados para promover o aumento de resolução axial de um fator de aproximadamente dois. Por fim uma análise crítica sobre os resultados e uma discussão sobre perspectivas dos temas abordados, foram realizada. / Tese (Doutoramento) / IPEN/T / Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP / FAPESP:09/13764-3

Medical imaging is critical for the detection and diagnosis of disease, guided biopsies, assessment of therapies, and administration of treatment. While computerized tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), and ultra-sound (US) are the more familiar modalities, interest in yet other modalities continues to grow. Among the motivations are reduction of cost, avoidance of ionizing radiation, and the search for new information, including biochemical and molecular processes. Fluorescence Molecular Tomography (FMT) is one such emerging technique and, like other techniques, has its advantages and limitations. FMT can reconstruct the distribution of fluorescent molecules in vivo using near-infrared radiation or visible band light to illuminate the subject. FMT is very safe since non-ionizing radiation is used, and inexpensive due to the comparatively low cost of the imaging system. This should make it particularly well suited for small animal studies for research. A broad range of cell activity can be identified by FMT, making it a potentially valuable tool for cancer screening, drug discovery and gene therapy. Since FMT imaging is scattering dominated, reconstruction of volume images is significantly more computationally intensive than for CT. For instance, to reconstruct a 32x32x32 image, a flattened matrix with approximately 10¹°, or 10 billion, elements must be dealt with in the inverse problem, while requiring more than 100 GB of memory. To reduce the error introduced by noisy measurements, significantly more measurements are needed, leading to a proportionally larger matrix. The computational complexity of reconstructing FMT images, along with inaccuracies in photon propagation models, has heretofore limited the resolution and accuracy of FMT. To surmount the problems stated above, we decompose the forward problem into a Khatri-Rao product. Inversion of this model is shown to lead to a novel reconstruction method that significantly reduces the computational complexity and memory requirements for overdetermined datasets. Compared to the well known SVD approach, this new reconstruction method decreases computation time by a factor of up to 25, while simultaneously reducing the memory requirement by up to three orders of magnitude. Using this method, we have reconstructed images up to 32x32x32. Also outlined is a two step approach which would enable imaging larger volumes. However, it remains a topic for future research. In achieving the above, the author studied the physics of FMT, developed an extensive set of original computer programs, performed COMSOL simulations on photon diffusion, and unavoidably, developed visual displays.

No description available.

La Tomographie Optique Diffuse (TOD) est une nouvelle technique d'imagerie médicale permettant de reconstruire les propriétés optiques des tissus biologiques dans le but de détecter des tumeurs cancéreuses. Il s’agit, toutefois, d’un problème inverse mal-posé et sous-déterminé. Le travail de cette thèse s’articule autour de la résolution de ce problème en utilisant l’équation du transfert radiatif comme modèle de propagation de la lumière (modèle direct). L’analyse de sensibilité a montré que le facteur d’anisotropie g de la fonction de phase de Henyey-Greenstein est le paramètre le plus influant sur la sortie du modèle direct suivi du coefficient de diffusion µs puis du coefficient d’absorption µa. Dans un premier temps, un algorithme de Gauss-Newton a été implémenté en utilisant les fonctions de sensibilités. Toutefois, ce dernier ne permet d’estimer qu'un nombre très limité de paramètres optiques (supposés constants en espace). Dans un second temps, un algorithme de Quasi-Newton a été développé pour reconstruire les distributions spatiales des propriétés optiques. Le gradient de la fonction objectif a été calculé efficacement par la méthode adjointe à travers le formalisme de Lagrange avec une approche Multi-fréquences. Les reconstructions sont obtenues à partir des données simulées en surface. Le facteur g est reconstruit comme un nouvel agent de contraste en TOD. Le problème de diaphonie entre µs g a été donc mis en évidence dans cette thèse. Notre algorithme a permis de reconstruire en 2D et 3D une ou plusieurs inclusions tumorales présentant différentes formes. La qualité des images reconstruites a été examinée en fonction du nombre de fréquences, de la diaphonie, du niveau de contraste (Inclusion/Fond), du niveau de bruit et de la position des inclusions tumorales / Diffuse Optical Tomography (DOT) is a new medical imaging technique used to reconstruct the optical properties of biological tissues in order to detect cancerous tumors. However, this is an ill-posed and under-determined inverse problem. The work of this thesis deals with the resolution of this problem using the radiative transfer equation as a forward model of light propagation. The sensitivity analysis showed that the anisotropy factor g of the Henyey-Greenstein phase function is the most sensitive parameter of the forward model followed by the scattering coefficient µs and then the absorption coefficient µa. In a first step, a Gauss-Newton algorithm was implemented using the sensitivity functions. However, this algorithm allows to estimate a very limited number of the optical parameters (assumed to be constant in space). In a second step, a Quasi-Newton algorithm was developed to reconstruct the spatial distributions of the optical properties. The gradient of the objective function was efficiently computed by the adjoint method through the Lagrangian formalism with a Multi-frequency approach. The reconstructed images were obtained from simulated boundary data. The g factor was reconstructed as a new optical contrast agent in DOT and the crosstalk problem between this factor and µs has been studied. The results showed that the algorithm is efficient to reconstruct in 2D and 3D one or several tumor inclusions having different shapes. The quality of the reconstructed images was examined according to several parameters: the number of frequencies, the crosstalk, the contrast and the noise levels